Heat exchange systems, devices and methods

ABSTRACT

Embodiments of the present invention relate generally to heat-exchanger systems that can be used to heat or cool a fluid such as blood. Pod pumps that provide low shear and low turbulence may be used in such systems, particularly for systems that pump blood. A certain heat-exchanger system used to heat blood or other fluids may be used to provide whole-body hyperthermic treatments or regional hyperthermic chemotherapy treatments. A disposable unit may be used to separate the fluid path from the fluid control systems. The disposable unit typically includes a heat-exchanger component that is received by a corresponding heat exchanger in a base unit. Fluid pumped through the heat-exchanger component is heated by the heat exchanger.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority from the following United StatesProvisional Patent Applications, all of which are hereby incorporatedherein by reference in their entireties:

U.S. Provisional Patent Application No. 60/792,073 entitledExtracorporeal Thermal Therapy Systems and Methods filed on Apr. 14,2006;

U.S. Provisional Patent Application No. 60/835,490 entitledExtracorporeal Thermal Therapy Systems and Methods filed on Aug. 4,2006;

U.S. Provisional Patent Application No. 60/904,024 entitled HemodialysisSystem and Methods filed on Feb. 27, 2007; and

U.S. Provisional Patent Application No. 60/921,314 entitled SensorApparatus filed on Apr. 2, 2007.

This application is also related to the following United States patentapplications, all of which are being filed on even date herewith and arehereby incorporated herein by reference in their entireties:

U.S. patent application entitled LIQUID PUMPING SYSTEM, DEVICE ANDMETHOD (Attorney Docket No. 1062/E78); and

U.S. patent application entitled THERMAL AND CONDUCTIVITY SENSINGSYSTEMS, DEVICES, AND METHODS (Attorney Docket No. 1062/E79).

This application is also related to U.S. patent application Ser. No.10/697,450 entitled BEZEL ASSEMBLY FOR PNEUMATIC CONTROL filed on Oct.30, 2003 and published as Publication No. US 2005/0095154 (AttorneyDocket No. 1062/D75) and related PCT Application No. PCT/US2004/035952entitled BEZEL ASSEMBLY FOR PNEUMATIC CONTROL filed on Oct. 29, 2004 andpublished as Publication No. WO 2005/044435 (Attorney Docket No.1062/D71 WO), both of which are hereby incorporated herein by referencein their entireties.

TECHNICAL FIELD

The present invention relates heat exchange systems

BACKGROUND ART

It is known in the prior art that altering the body temperature of apatient by means of extracorporeal heating can treat a variety ofdiseases, such as Hepatitis C and possibly some types of cancer,HIV/AIDS, rheumatoid arthritis and psoriasis. In order to heat the bloodin a reasonable amount of time, high flow rates are necessary from thepatient's body to a heater and back to the patient.

Centrifugal pumps have been used in prior art systems in order toachieve relatively large flow rates of blood to and from the patient'sbody. Although the centrifugal pumps can achieve the necessary high flowrates, the centrifugal pumps create relatively large shear forces on theblood resulting in an undesirable amount of hemolysis. Heated blood iseven more prone to hemolysis.

Because of the large flow rates of blood to and from the patient, a leakin the system could quickly result in the death of the patient.

The prior art systems also typically involve bulky equipment and arerelatively clumsy, resulting in time lags when switching the system fromone patient to the next, and increasing the risk of the system beingimproperly set up.

SUMMARY OF THE INVENTION

In accordance with one aspect of the invention there is provided amethod for heating or cooling a fluid, the method comprising:

providing at least one reciprocating positive-displacement pump, eachpump having:

-   -   a curved rigid chamber wall;    -   a flexible membrane attached to the rigid chamber wall, so that        the flexible membrane and rigid chamber wall define a pumping        chamber;    -   an inlet for directing fluid through the rigid chamber wall into        the pumping chamber in at least one of (a) a direction that is        substantially tangential to the rigid chamber wall and (b) a        direction that provides low-shear flow into the pumping chamber;        and    -   an outlet for directing fluid through the rigid chamber wall out        of the pumping chamber in at least one of (a) a direction that        is substantially tangential to the rigid chamber wall and (b) a        direction that provides low-shear flow out of the pumping        chamber;

providing a heat exchanger; and

pumping the fluid from a source using the at least one reciprocatingpositive-displacement pump so as to cause the fluid to pass through theheat exchanger.

In accordance with another aspect of the invention there is provided adisposable unit for use in a heat exchanger system, the disposable unitcomprising:

at least one reciprocating positive-displacement pump, each pump having

-   -   a curved rigid chamber wall;    -   a flexible membrane attached to the rigid chamber wall, so that        the flexible membrane and rigid chamber wall define a pumping        chamber;    -   an inlet for directing fluid through the rigid chamber wall into        the pumping chamber in at least one of (a) a direction that is        substantially tangential to the rigid chamber wall and (b) a        direction that provides low-shear flow into the pumping chamber;        and    -   an outlet for directing fluid through the rigid chamber wall out        of the pumping chamber in at least one of (a) a direction that        is substantially tangential to the rigid chamber wall and (b) a        direction that provides low-shear flow out of the pumping        chamber; and

a heat-exchanger component, in fluid communication with the at least onepump and adapted to be received by a heat exchanger.

In accordance with another aspect of the invention there is provided aheat-exchanger system comprising:

a heat exchanger for receiving a heat-exchanger component of adisposable unit;

a pneumatic actuation system for operating at least one pump of thedisposable unit for pumping fluid through the heat-exchanger component;and

a controller for controlling the pneumatic actuation system.

In some embodiments, the disposable unit may be considered to be part ofthe heat-exchanger system.

In accordance with another aspect of the invention there is provided amethod of moving blood between a patient-access device and a heatexchanger for heating the blood, the method comprising:

providing a reciprocating positive-displacement pump;

providing a flow line having a first portion between the patient-accessdevice and the pump and having a second portion between the pump and theheat exchanger;

providing for each of the first and second portions of the flow line avalve for permitting flow in only one direction of the flow line; and

actuating the pump to cause the flow of blood between the patient-accessdevice and the heat exchanger.

In accordance with another aspect of the invention there is provided asystem for extracorporeal thermal therapy, the system comprising:

a heat exchanger for heating the blood;

a reciprocating positive-displacement pump for moving blood between apatient-access device and the heat exchanger, the pump having an inletline and an outlet line;

a first valve, located in the inlet line, for preventing flow of bloodout of the pump; and

a second valve, located in the outlet line, for preventing flow of bloodinto the pump.

In accordance with another aspect of the invention there is provided aheat exchanger for heating extracorporeal blood for hyperthermiatreatment, the heat exchanger comprising a pump according to one ofabove claims, and further including a heat-exchange flow path having aninlet for unheated blood an outlet for heated blood;

an electricity-to-heat converter that turns electrical power into heatfor absorption by the blood;

a first temperature sensor located at the inlet for measuring thetemperature of the blood entering the heat exchanger;

a second temperature sensor located at the outlet for measuring thetemperature of the blood exiting the heat exchanger;

a metering system that measures the flow rate of blood passing throughthe heat exchanger; and

a controller in communication with the converter, the first and secondtemperature sensors, and the metering system, the controller receivinginformation regarding the amount of power being used by the converter,receiving temperature information from the first and second temperaturesensors, receiving flow-rate information from the metering system,analyzing the received information in order to determine whether a faultcondition exists, and generating a signal if a fault condition isdetected.

In accordance with another aspect of the invention there is provided aheat exchanger for heating extracorporeal blood for hyperthermiatreatment, the heat exchanger comprising:

an inlet for unheated blood;

an outlet for heated blood;

a flow path from the inlet to the outlet;

a set of heating elements overlapping the flow path, including at leastfirst and second heating elements, the second heating element beinglocated adjacent the flow path near the outlet, and the first heatingelement being located adjacent the flow path at a point upstream of thesecond heating element;

a first temperature sensor located adjacent the flow path upstream ofthe first heating element;

a second temperature sensor located adjacent the flow path between thefirst and second heating elements; and

a controller for receiving temperature information from the first andsecond temperature sensors and for generating a signal if a temperaturedifference being measured by the first and second sensors exceeds alimit.

In accordance with another aspect of the invention there is provided aheat exchanger for heating extracorporeal blood for hyperthermiatreatment, the heat exchanger comprising:

an inlet for unheated blood;

an outlet for heated blood;

a flow path from the inlet to the outlet;

a set of heating elements overlapping the flow path, including at leastfirst, second and third heating elements, the third heating elementbeing located adjacent the flow path near the outlet, the second heatingelement being located adjacent the flow path at a point prior to thethird heating element, and the first heating element being locatedadjacent the flow path at a point prior to the second heating element;

a first temperature sensor located adjacent the flow path between thefirst and second heating elements;

a second temperature sensor located adjacent the flow path between thesecond and third heating elements; and

a controller for receiving temperature information from the first andsecond temperature sensors and for generating a signal if a temperaturedifference being measured by the first and second sensors exceeds alimit.

In accordance with another aspect of the invention there is provided aheat exchanger for heating extracorporeal blood for hyperthermiatreatment, the heat exchanger comprising:

an inlet for unheated blood;

an outlet for heated blood;

an electricity-to-heat converter that turns electrical power into heatfor absorption by the blood;

a first temperature sensor located at the inlet for measuring thetemperature of the blood entering the heat exchanger;

a second temperature sensor located at the outlet for measuring thetemperature of the blood exiting the heat exchanger;

a metering system that measures the flow rate of blood passing throughthe heat exchanger; and

a controller in communication with the converter, the first and secondtemperature sensors, and the metering system, the controller receivinginformation regarding the amount of power being used by the converter,receiving temperature information from the first and second temperaturesensors, receiving flow-rate information from the metering system,analyzing the received information in order to determine whether a faultcondition exists, and generating a signal if a fault condition isdetected.

In accordance with another aspect of the invention there is provided aheat exchanger for heating extracorporeal blood for hyperthermiatreatment, the heat exchanger comprising:

an inlet for unheated blood;

an outlet for heated blood;

an electricity-to-heat converter that turns electrical power into heatfor absorption by the blood;

a disposable unit containing a flow path of the blood from the inlet tothe outlet, the disposable unit being made primarily of a thermoplasticmaterial;

an electrical-conductivity sensor for measuring the resistance betweenthe blood in the flow path a thermowell and the converter; and

a controller in communication with the electrical-conductivity sensorand generating a signal if the measured resistance does not satisfy asafety parameter.

In accordance with another aspect of the invention there is provided aheat exchanger for heating extracorporeal blood for hyperthermiatreatment, the heat exchanger comprising:

a disposable unit having

-   -   an inlet for unheated blood,    -   an outlet for heated blood, and    -   a flow path of the blood from the inlet to the outlet; and

a base unit having

a heater for heating blood in the flow path, the heater including afirst thermally conductive plate for conducting heat to a first side ofthe disposable unit, and a second thermally conductive plate forconducting heat to a second side of the disposable unit opposite thefirst plate, the first and second plates being adapted to squeezetogether, upon actuation by a controller, in order to urge blood out ofthe disposable.

In accordance with another aspect of the invention there is provided amethod of locating temperature probes for monitoring a patient'stemperature, the method comprising:

taking temperature readings from a first temperature probe to be locatedat a first location in the patient's body;

taking temperature readings from a second temperature probe to belocated at a second location in the patient's body;

comparing the temperature readings from the first and second probes;

positioning the first and second temperature probes in the patient'sbody;

determining if the temperature reading from the first or second locationis above a pre-set limit; and

generating a placement signal, if the temperature reading from the firstprobe is within a pre-set range from the temperature reading from thesecond probe, and if the reading from the first or second location isabove a pre-set limit.

In accordance with another aspect of the invention there is provided amethod of providing a hyperthermic treatment to a patient, the methodcomprising:

providing a heat-exchanger system for heating blood from the patient andpumping heated blood to the patient;

connecting a first temperature probe from the patient to theheat-exchanger system, the heat-exchanger system controlling the bloodheating and pumping based on temperature information received from thefirst temperature probe and displaying the temperature informationreceived from the first temperature probe to an operator;

monitoring patient temperature by the operator using an independentsecond temperature probe; and

-   -   terminating the treatment if either of the temperature probes        conveys an unacceptable temperature reading.

In some embodiments of the invention there is provided a pump-podgeometry that reduces shear on the fluid being pumped and, when used topump blood (especially heated blood), reduces hemolysis.

In one embodiment of the invention, a reciprocatingpositive-displacement pump is provided with a hemispherical rigidchamber wall; a flexible membrane attached to the rigid chamber wall, sothat the flexible membrane and rigid chamber wall define a pumpingchamber; an inlet for directing flow through the rigid chamber wall intothe pumping chamber in a direction that provides low-shear flow into thepumping chamber; and an outlet for directing flow through the rigidchamber wall out of the pumping chamber in a direction that provideslow-shear flow out of the pumping chamber.

In one embodiment of the invention, a reciprocatingpositive-displacement pump is provided comprising a rigid hemisphericalchamber wall; a flexible membrane attached to the rigid chamber wall, sothat the flexible membrane and rigid chamber wall define a pumpingchamber; an inlet for directing flow through the rigid chamber wall intothe pumping chamber in a direction that is substantially tangential tothe rigid chamber wall; and an outlet for directing flow through therigid chamber wall out of the pumping chamber in a direction that issubstantially tangential to the rigid chamber wall. In some embodiments,the reciprocating positive-displacement pump also includes a rigid limitstructure for limiting movement of the membrane and limiting the maximumvolume of the pumping chamber, the flexible membrane and the rigid limitstructure defining an actuation chamber. The rigid limit structure maybe adapted to limit movement of the flexible membrane such that, whenthe pumping chamber is at maximum volume, the rigid chamber and theflexible membrane (which will be urged against the rigid limitstructure) define the pumping chamber as a spherical volume. The rigidlimit structure may be a hemispherical limit wall that, together withthe flexible membrane, defines a spherical actuation chamber when thepumping chamber is at minimum volume.

In certain embodiments, the reciprocating positive-displacement pump isprovided with a pneumatic actuation system that intermittently provideseither a positive or a negative pressure to the actuation chamber. Thepneumatic actuation system in some embodiments include a reservoircontaining a gas at either a positive or a negative pressure, and avalving mechanism for controlling the flow of gas between the actuationchamber and the gas reservoir. The reciprocating positive-displacementpump may be provided with an actuation-chamber pressure transducer formeasuring the pressure of the actuation chamber, and a controller thatreceives pressure information from the actuation-chamber pressuretransducer and controls the valving mechanism. In certain embodiments, areservoir pressure transducer for measuring the pressure of the pressureof gas in the reservoir is provided, and the controller receivespressure information from the reservoir pressure transducer. Thecontroller in some embodiments compares the pressure information fromthe actuation-chamber and reservoir pressure transducers to determinewhether either of the pressure transducers is malfunctioning.

In certain embodiments, the pneumatic actuation system alternatelyprovides positive and negative pressure to the actuation chamber. In onearrangement, the pneumatic actuation system includes a positive-pressuregas reservoir, a negative-pressure gas reservoir, and a valvingmechanism for controlling the flow of gas between the actuation chamberand each of the gas reservoirs. In such embodiments, anactuation-chamber pressure transducer is also provided for measuring thepressure of the actuation chamber, and a controller that receivespressure information from the actuation-chamber pressure transducer andcontrols the valving mechanism. In addition, such embodiments mayinclude a positive-pressure-reservoir pressure transducer for measuringthe pressure of the positive-pressure gas reservoir, and anegative-pressure-reservoir pressure transducer for measuring thepressure of the negative-pressure gas reservoir. The controller receivespressure information from these transducers and analyzes the pressureinformation to determine whether any of the pressure transducers aremalfunctioning. The controller also controls the pressure of thereservoir or reservoirs to ensure it does not exceed a pre-set limit.

In certain embodiments, the controller causes dithering of the valvingmechanism and determines when a stroke ends from pressure informationfrom the actuation-chamber pressure transducer. In further embodiments,the controller controls the valving mechanism to cause the flexiblemembrane to reach either the rigid chamber wall or the rigid limitstructure at each of a stroke's beginning and end. In this embodiment,the controller can determine the amount of flow through the pump basedon a number of strokes. In addition, the controller may integratepressure information from the actuation-chamber pressure transducer overtime during a stroke (or otherwise determines the work done during astroke) as a way of detecting an aberrant flow condition.

In some embodiments of the invention, the reciprocatingpositive-displacement pump includes an inlet valve for preventing flowout of the pump and an outlet valve for preventing flow into the pump.In some embodiments, these valves are simply passive check valves, andin other embodiments, these valves are active valves that are controlledto cause fluid to flow in the desired direction. In certain embodiments,the pump is adapted for pumping a liquid, and in further embodiments,the pump is adapted for pumping a biological liquid, such as blood. Asnoted above, some embodiments of the inventions are well adapted forpumping heated blood.

In certain embodiments, the pumps are paired—or otherwiseganged—together so that an inlet line leads to both pumps' inlets andwherein an outlet line leads from both pumps' outlets. In suchembodiments, the pumps may be operated out of phase such that when onepump's pumping chamber is substantially full the other pump's pumpingchamber is substantially empty.

Embodiments of the invention also provide methods for heating bloodextracorporeally. One method includes the steps of providing areciprocating positive-displacement pump; providing a flow line having afirst portion between the patient-access device and the pump and havinga second portion between the pump and a heat exchanger; providing foreach of the first and second portions of the flow line a valve forpermitting flow in only one direction of the flow line; and actuatingthe pump to cause the flow of blood between the patient-access deviceand the heat exchanger. The pump may be provided with a flexiblemembrane as a reciprocating member. A pneumatic actuation system may beprovided for alternately providing positive and negative pressure to themembrane. A pump having one of the various structures described hereinmay be used in such methods.

Certain methods for heating blood extracorporeally include the steps ofproviding a reciprocating positive-displacement pump having a curvedrigid chamber wall, a flexible membrane attached to the rigid chamberwall so that the flexible membrane and rigid chamber wall define apumping chamber, an inlet for directing flow through the rigid chamberwall into the pumping chamber in a direction that is substantiallytangential to the rigid chamber wall, and an outlet for directing flowthrough the rigid chamber wall out of the pumping chamber in a directionthat is substantially tangential to the rigid chamber wall; providing aheater; providing blood from a source; and pumping the blood using thereciprocating positive-displacement pump so as to cause the blood toflow through the heater and be heated. The reciprocatingpositive-displacement pump is, in certain embodiments, provided with thestructural features discussed herein.

Certain embodiments of these methods include the step of monitoring thepatient's temperature. Monitoring the patient's temperature may includethe steps of taking a temperature reading from a first location in thepatient's body; taking a temperature reading from a second location inthe patient's body; comparing the temperature readings from the firstand second locations; generating a first alarm signal indicating faultytemperature readings, if the temperature reading at the first locationis not within a pre-set range from the temperature reading at the secondlocation; determining if the temperature reading from the first locationis above a pre-set upper limit; and generating a second alarm signalindicating an overheated condition, if a reading is above the pre-setupper limit.

The methods described herein may use a disposable unit for use in asystem for heating blood extracorporeally. Such disposable units mayinclude a reciprocating positive-displacement pump having a curved rigidchamber wall, a flexible membrane attached to the rigid chamber wall sothat the flexible membrane and rigid chamber wall define a pumpingchamber, an inlet for directing flow through the rigid chamber wall intothe pumping chamber in a direction that is substantially tangential tothe rigid chamber wall, and an outlet for directing flow through therigid chamber wall out of the pumping chamber in a direction that issubstantially tangential to the rigid chamber wall; and a heat-exchangercomponent, in fluid communication with the pump, and adapted to bereceived by a heater. The heat-exchanger component may include aflexible bag that defines a flow path therethrough. The reciprocatingpositive-displacement pump may have a structure as described herein.

The disposable unit preferably attaches, in an easily removable manner,to a base unit, which preferably includes means for attaching to apneumatic actuation system that intermittently provides either apositive or a negative pressure to the pump's actuation chamber, andpreferably includes the controller for controlling the pneumaticactuation system. The controller preferably controls the system so as toperform methods described herein. The base unit is preferably capable ofreceiving and holding disposable units having pod pumps with differentstroke volumes

In one embodiment of a system for extracorporeal thermal therapy, a heatexchanger is provided for heating the blood; a reciprocatingpositive-displacement pump is provided for moving blood between apatient-access device (e.g., a cannula, needle or shunt) and the heatexchanger, the pump having an inlet line and an outlet line; a firstvalve, located in the inlet line, is provided for preventing flow ofblood out of the pump; and a second valve, located in the outlet line,is provided for preventing flow of blood into the pump. The pump mayhave a structure as described herein.

In a particular embodiment, the reciprocating positive-displacement pumpuses a flexible membrane made from a material that reduces hard snappingof the membrane as the membrane reciprocates. The central portion mayinclude bumps that space the central portion away from the rigid chamberwall when the membrane is in a minimum-pumping-chamber-volume position.Such bumps prevent liquid from being trapped between the membrane andthe wall.

The controller, in a particular embodiment, receives temperatureinformation from a first temperature sensor located at the inlet formeasuring the temperature of the blood entering the heat exchanger andfrom a second temperature sensor located at the outlet for measuring thetemperature of the blood exiting the heat exchanger, while alsoreceiving flow-rate information from a metering system that measures theflow rate of blood passing through the heat exchanger. These temperaturesensors may be located in a base unit of the system, while thermallyconductive thermowells in the disposable unit provide thermalcommunication between the flow path and the base unit's sensors. Thecontroller is also in communication with an electricity-to-heatconverter and receives information regarding the amount of power beingused by the converter. The controller, in this embodiment, analyzes thereceived information from the temperature probes, the metering systemand the converter in order to determine whether a fault conditionexists, and generates a signal if a fault condition is detected.

The controller may also receive temperature information from temperaturesensors mounted near heating elements adjacent the heat exchanger'sheating plates, wherein electrical current causes the heating elementsto heat the heating plates, which in turn heat the blood passing throughthe heat exchanger. A set of heating elements may overlap the flow paththrough the heat exchanger. The set of heating elements includes atleast first and second heating elements, the second heating elementbeing located adjacent the flow path near the outlet, and the firstheating element being located adjacent the flow path at a point upstreamof the second heating element. A first temperature sensor is locatedadjacent the flow path upstream of the first heating element, and asecond temperature sensor is located adjacent the flow path between thefirst and second heating elements. In this embodiment, the controllerreceives temperature information from the first and second temperaturesensors, and generates a signal if a temperature difference beingmeasured by the first and second sensors exceeds a limit. Of course, theheat exchanger may use additional heating elements beyond the tworeferred to here. The flow path may course through a substantiallyplanar disposable unit. This disposable unit, as noted above, may be aflexible bag.

A first heating plate, which in one embodiment is simply a thermallyconductive plate, may be located between the heating elements and thedisposable unit. A second heating plate may be located adjacent thedisposable unit opposite the first heating plate, and a second set ofheating elements may be located on a side of the second plate oppositethe disposable unit and overlapping the flow path, including at leastfourth, fifth and sixth heating elements, the sixth heating elementbeing located adjacent the flow path near the outlet, the fifth heatingelement being located adjacent the flow path at a point prior to thesixth heating element, and the fourth heating element being locatedadjacent the flow path at a point prior to the fifth heating element. Inthis embodiment, a third temperature sensor may be located adjacent theflow path between the fourth and fifth heating elements, and a fourthtemperature sensor is located adjacent the flow path between the fifthand sixth heating elements. The controller also receives temperatureinformation from the third and fourth temperature sensors and generatesa signal if a temperature difference being measured by the third andfourth sensors exceeds a limit. In one embodiment, the first and secondplates may be adapted to squeeze together, upon actuation by thecontroller, in order to urge blood out of the disposable.

In a certain embodiment, the thermowells referred to previously may alsobe electrically conductive and be used to detect leaks or air in thesystem. The disposable unit adapted to be received by the heat exchangerand containing a flow path of the blood may be made primarily of athermoplastic material. The thermowells located at each of the inlet andoutlet are preferably metal to improve thermal and electricalconductivity between the first temperature sensor and the blood in theinlet and between the second temperature sensor and the blood in theoutlet. The heating plates each typically include anelectrical-conductivity sensor for measuring the resistance between athermowell and a plate. The controller is in communication with theelectrical-conductivity sensor and generates a signal if the measuredresistance is too low (indicating a leak in the disposable unit) and/ortoo high (indicating air in the disposable unit).

In a certain embodiment, a valving system is provided. The valvingsystem includes a valve cassette and a control cassette. The valvecassette contains a plurality of valves, each valve including a valvingchamber and an actuation chamber, each valve being actuatable by acontrol fluid in the actuation chamber. The control cassette has aplurality of fluid-interface ports for providing fluid communicationwith a control fluid from a base unit. A plurality of tubes extendsbetween the valve cassette and the control cassette. Each tube providesfluid communication between a fluid-interface port and at least oneactuation chamber, such that the base unit can actuate a valve bypressurizing control fluid in a fluid interface port.

These aspects of the invention are not meant to be exclusive orcomprehensive and other features, aspects, and advantages of the presentinvention are possible and will be readily apparent to those of ordinaryskill in the art when read in conjunction with the followingdescription, the appended claims, and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing features of the invention will be more readily understoodby reference to the following detailed description, taken with referenceto the accompanying drawings, wherein:

FIG. 1 is a perspective view of an extracorporeal-blood-heating systemhaving a base unit with a disposable unit according to one embodiment ofthe invention;

FIG. 2 is a perspective view of components of the disposable unit shownin FIG. 1;

FIG. 3 is a perspective view of a pump pod of the disposable unit shownin FIG. 2;

FIG. 4 is a schematic showing a pressure actuation system that may beused to actuate the pump pod shown in FIG. 3;

FIGS. 5A and 5B are respectively upper and lower perspective views of analternative embodiment of a pump pod arrangement;

FIG. 6 is a schematic of an embodiment of the extracorporeal bloodheating system;

FIGS. 7 and 8 are graphs showing how pressure measurements can be useddetect the end of a stroke, in one embodiment;

FIGS. 9 and 10 show how the pressure-measurement signals are filtered bythe system's controller;

FIG. 11 is a graph showing pressure readings in each of the pump pods inthe disposable unit, and the results of filtering these readings;

FIG. 12 is a graph showing how pressure measurements are used todetermine average pressure;

FIG. 13A is a perspective view of the components from the system of FIG.1 used for transferring heating to the blood;

FIG. 13B is a perspective, back-side cross-sectional view of themanifold of FIGS. 2 and 49, in accordance with an exemplary embodimentof the present invention;

FIG. 13C shows a thermowell that may be used in the manifold of FIGS. 2,49, and 13B in the heat-exchanger figure of FIG. 1, in accordance withan exemplary embodiment of the present invention;

FIG. 14 is an exploded view showing the basic components of a heatexchanger in an alternative embodiment;

FIGS. 15, 16 and 17 show respectively top perspective, end perspectiveand top plan views of the disposable unit's heat-exchanger bag used inthe heat exchanger shown in FIG. 14;

FIG. 18 shows a preferred placement of temperature transducers in a heatexchanger;

FIG. 19 is a flow chart showing a method for checking a patient'stemperature;

FIG. 20 is a sectional view of a pod-pump that may be incorporated intoembodiments of fluid-control cassettes;

FIG. 21 is a sectional view of a valve that may be incorporated intoembodiments of fluid-control cassettes;

FIGS. 22A and 22B shows a pump cassette incorporating two pump pods ofthe type shown in FIG. 20 and a number of valves of the type shown inFIG. 21 along with various fluid paths and other components, inaccordance with an exemplary embodiment of the present invention;

FIG. 23 is a schematic representation of dual-housing cassettearrangement according to one embodiment;

FIG. 24 is a schematic view of a whole-body hyperthermic treatmentsystem in accordance with an exemplary embodiment of the presentinvention;

FIG. 25 shows the base unit of FIG. 1, in accordance with an exemplaryembodiment of the present invention;

FIG. 26 shows a close-up view of the manifold interface of FIG. 25, inaccordance with an exemplary embodiment of the present invention;

FIG. 27 shows an exemplary user interface screen in accordance with anexemplary embodiment of the present invention;

FIG. 28 is a graph showing how pressures applied to a pod pump may becontrolled in order to facilitate end-of-stroke detection, in accordancewith an exemplary embodiment of the present invention;

FIG. 29 is a schematic representation of circulatory fluid flow in thepump pod shown in FIG. 3, in accordance with an exemplary embodiment ofthe present invention;

FIGS. 30A and 30B are top and section views of a modular pod pump;

FIGS. 31A and 31B are top and section views of a pod pump with separateinlet and outlet ports, FIG. 31A showing a section line to indicate theview in FIG. 31B;

FIGS. 32A and 32B are top and section views of a pod pump with an insertin the actuation chamber;

FIGS. 33A and 33B are top and section views of a pod pump with alaminated construction;

FIGS. 34A and 34B are top and section views of a pod pump with alaminated construction;

FIG. 35A is an exploded pictorial view of a pod pump with a multi parthousing; FIGS. 35B-E are pictorial views of various embodiments ofdiaphragms;

FIGS. 36A and 36B are side and end views of an assembled pod pump with amulti part housing;

FIG. 36C is a close up view of a port on a pod pump with a multi parthousing;

FIG. 37 is an exploded pictorial view of a multi part pod pump housing;

FIGS. 38A and 38B are top and section views of a pod pump assembly withintegral valves;

FIG. 39 is an exploded pictorial view of a pod pump assembly;

FIG. 40A is a pictorial view of two parts of a multi part pod pumphousing;

FIG. 40B is a pictorial closeup view of aligning features on parts of amulti part pump housing;

FIG. 41A is a pictorial section view of a pod pump assembly with someportions removed;

FIG. 41B is a close up pictorial view of aligning and joining featureson a pod pump housing;

FIG. 42A is a pictorial view of a pod pump;

FIG. 42B is a sectional view of the pod pump shown in FIG. 42A;

FIG. 42C is a pictorial view of a pod pump;

FIG. 42D is a sectional view of the pod pump shown in FIG. 42C;

FIGS. 43A-43C are exploded and section views of one embodiment of a podpump cassette;

FIGS. 44A-44B are pictorial views of one embodiment of a pod pumpcassette;

FIG. 45 shows a representation of a regional hyperthermic chemotherapytreatment system in accordance with an exemplary embodiment of thepresent invention;

FIGS. 46A and 46B respectively show upper and lower perspective views ofa flexible membrane having a configuration of raised bumps, such as maybe used in pump pods such as the in the pump pod of FIG. 4, inaccordance with an exemplary embodiment of the present invention;

FIG. 47A shows some of the interior components of the base unit of FIGS.1 and 25, in accordance with an exemplary embodiment of the presentinvention;

FIG. 47B shows a rear perspective view of the base unit of FIGS. 1 and25 showing patient interfaces, in accordance with an exemplaryembodiment of the present invention;

FIG. 48 shows an exemplary disposable unit in accordance with anexemplary embodiment of the present invention;

FIGS. 49A and 49B respectively show a perspective back-side view and aperspective bottom view of the manifold from FIG. 2, in accordance withan exemplary embodiment of the present invention;

FIGS. 50A and 50B are embodiments of the sensing apparatus where thethermal well is a continuous part of the fluid line;

FIGS. 51A and 51B are embodiments of the sensing apparatus where thethermal well is a separate part from the fluid line;

FIGS. 52A and 52B are embodiments of the sensing apparatus showingvarious lengths and widths of the thermal well;

FIG. 53 is a pictorial view of a thermal well according to oneembodiment of the sensing apparatus;

FIG. 54 is a cross sectional view of an exemplary embodiment of thethermal well;

FIGS. 55A and 55B show section views of embodiments of thermal wellshaving variable wall thickness;

FIGS. 56A-56S are sectional views of various embodiments of the thermalwell embedded in a fluid line;

FIG. 57 is a section side view of one embodiment of the sensing probe;

FIG. 58 is an exploded view of the embodiment shown in FIG. 8;

FIG. 59 is a sectional view of an alternate embodiment of the tip of thesensing probe;

FIG. 60A is an alternate embodiment of the sensing probe;

FIG. 60B is an alternate embodiment of the sensing probe;

FIG. 61 is a side view of an alternate embodiment of the sensing probe;

FIG. 62A is a section view of a sensing probe coupled to a thermal well;

FIG. 62B is an alternate embodiment of the sensing probe shown in FIG.13A;

FIG. 63A is a section view of a sensing probe as shown in FIG. 8 coupledto a thermal well;

FIG. 63B is an alternate embodiment of the sensing probe shown in FIG.14A;

FIG. 64 is a sectional view of one exemplary embodiment of the sensorapparatus;

FIG. 65 shows an alternate embodiment of a sensing probe coupled to athermal well;

FIG. 66 is a section view of one embodiment of a sensing probe coupledto a thermal well and suspended by a spring;

FIG. 67 is a section view of one embodiment of a sensing probe in ahousing;

FIG. 68 is a section view of one embodiment of a sensing probe in ahousing;

FIG. 69 is a section view of one embodiment of a sensing probe in ahousing;

FIG. 70 is a side view of a fluid line including two sensors;

FIG. 71 is a section view of a fluid line with a sensor apparatus;

FIG. 72 shows one way in which the various components of the disposableunit of FIG. 2 can be interconnected;

FIGS. 73A-73B are graphical representations of occlusion detection inaccordance with an exemplary embodiment of the present invention;

FIGS. 74A-74C show plots for volume flow, pod volumes, and total hold upflow for two pump pods operating in a zero degree phase relationship, a180 degree phase relationship, and a 90 degree phase relationship,respectively, in accordance with exemplary embodiments of the presentinvention

FIG. 75 shows a radiator for use with a length of tubing, in accordancewith an exemplary embodiment of the present invention;

FIG. 76 shows a length of flexible tubing install in the radiator ofFIG. 75 in accordance with an exemplary embodiment of the presentinvention;

FIG. 77 shows a heat exchanger plate having guides for receiving theradiator of FIG. 75, in accordance with an exemplary embodiment of thepresent invention;

FIG. 78 shows a heat exchanger plate having a cylindrical wall forreceiving the radiator of FIG. 75, in accordance with an exemplaryembodiment of the present invention;

FIG. 79 shows a heat exchanger plate having an integral radiator of thetype shown in FIG. 75, in accordance with an exemplary embodiment of thepresent invention;

FIG. 80 shows an enclosed radiator having fluid inlet and outlet ports,in accordance with an alternate embodiment of the present invention;

FIG. 81 shows a variation of the disposable unit of FIG. 48 including apatient connection circuit having a sterile protective covering, inaccordance with an exemplary embodiment of the present invention;

FIG. 82 shows a representation of the patient connection circuit fromFIG. 81 with a portion of tubing exposed through the sterile protectivecovering, in accordance with an exemplary embodiment of the presentinvention; and

FIG. 83 shows a variation of the disposable unit of FIG. 81 including anadditional fluid delivery line, in accordance with an exemplaryembodiment of the present invention;

FIG. 84 shows a fluid circuit that may be used for providing regionalhyperthermic chemotherapy treatment, in accordance with an exemplaryembodiment of the present invention;

FIG. 85 shows another fluid circuit including a balancing chamber thatmay be used for providing regional hyperthermic chemotherapy treatment,in accordance with an exemplary embodiment of the present invention;

FIG. 86 shows another fluid circuit including a balancing chamber and asecond pump that may be used for providing regional hyperthermicchemotherapy treatment, in accordance with an exemplary embodiment ofthe present invention; and

FIG. 87 shows a fluid circuit including a drain valve that may be usedfor providing regional hyperthermic chemotherapy treatment, inaccordance with an exemplary embodiment of the present invention.

It should be noted that the foregoing figures and the elements depictedtherein are not necessarily drawn to consistent scale or to any scale.Unless the context otherwise suggests, like elements are indicated bylike numerals.

DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS

Definitions. As used in this description and the accompanying claims,the following terms shall have the meanings indicated, unless thecontext otherwise requires:

“Spheroid” means any three-dimensional shape that generally correspondsto a oval rotated about one of its principal axes, major or minor, andincludes three-dimensional egg shapes, oblate and prolate spheroids,spheres, and substantially equivalent shapes.

“Hemispheroid” means any three-dimensional shape that generallycorresponds to approximately half a spheroid.

“Spherical” means generally spherical.

“Hemispherical” means generally hemispherical.

“Dithering” a valve means rapidly opening and closing the valve.

“Pneumatic” means using air or other gas to move a flexible membrane orother member.

“Substantially tangential” means at an angle less than 75° to a tangent,or in the case of a flat wall, at an angle of less than 75° to the wall.

“Fluid” shall mean a substance, a liquid for example, that is capable ofbeing pumped through a flow line. Blood is a specific example of afluid.

“Impedance” shall mean the opposition to the flow of fluid.

A “patient” includes a person or animal from whom, or to whom, fluid ispumped, whether as part of a medical treatment or otherwise.

“Subject media” is any material, including any fluid, solid, liquid orgas, that is in contact with either a sensing probe or a thermal well.

Various aspects of the present invention are described below withreference to various exemplary embodiments. It should be noted thatheadings are included for convenience and do not limit the presentinvention in any way.

1. Exemplary Reciprocating Positive-Displacement Pumps

Embodiments of the present invention relate generally to certain typesof reciprocating positive-displacement pumps (which may be referred tohereinafter as “pods,” “pump pods,” or “pod pumps”) used to pump fluids,such as a biological fluid (e.g., blood or peritoneal fluid), atherapeutic fluid (e.g., a medication solution), or a surfactant fluid.Certain embodiments are configured specifically to impart low shearforces and low turbulence on the fluid as the fluid is pumped from aninlet to an outlet. Such embodiments may be particularly useful inpumping fluids that may be damaged by such shear forces (e.g., blood,and particularly heated blood, which is prone to hemolysis) orturbulence (e.g., surfectants or other fluids that may foam or otherwisebe damaged or become unstable in the presence of turbulence).

Generally speaking, the pod pump is a modular pump apparatus. The podpump can be connected to any subject fluid (i.e., liquid, gas orvariations thereof) source, which includes but is not limited to a path,line or fluid container, in order to provide movement of said subjectfluid. In some embodiments, multiple pod pumps are used, however, inother embodiments, one pod pump is used. The pod pump can additionallybe connected to at least one actuation source, which in someembodiments, is at least one air chamber. In some embodiments, the podpump is modularly connected to any device or machine. However, in otherembodiments, the pod pump is part of a device, machine or container thatis attached to another device, machine or container. Although the podpump is modular, the pod pump may also be part of another modularstructure that interacts with any machine, device, container orotherwise.

In one embodiment, the pod pump includes a housing having a diaphragm ormovable impermeable membrane attached to the interior of the housing.The diaphragm creates two chambers. One chamber does not come intocontact with subject fluid; this chamber is referred to as the actuationchamber. The second chamber comes into contact with the subject fluid.This chamber is referred to as the pump or pumping chamber.

The pod pump, in some embodiments, includes an inlet fluid path and anoutlet fluid path. Thus, in these embodiments, a subject fluid is pumpedinto the pump chamber, then out of the pump chamber. In someembodiments, valving mechanisms are used to ensure that the fluid movesin the intended direction. In other embodiments, the inlet fluid pathand the outlet fluid path are one in the same.

The actuation of the diaphragm is provided for by a change in pressure.This change in pressure can be created through use of positive andnegative air pressures. In one embodiment, a pneumatic mechanism is usedto fill the actuation chamber with air (creating a positive pressure)and then to suck the air out of the actuation chamber (creating anegative pressure). In some embodiments, the air flows through a port inthe actuation chamber. The port can be, but is not limited to, anopening or aperture in the actuation chamber. In other embodiments, anyfluid (i.e., liquid, gas or variations thereof) can be used as anactuation fluid.

For purposes of this description, exemplary embodiments are shown anddescribed. However, other embodiments are contemplated, thus, thedescription provided are meant to bring an understanding of the pod pumpembodiments, other variations will be apparent.

1.1. Exemplary Pump Pod Configurations

FIG. 3 shows a reciprocating positive-displacement pump 25 in accordancewith an exemplary embodiment of the present invention. In thisembodiment, the reciprocating positive-displacement pump 25 isessentially a self-contained unit (which may be referred to hereinafteras a “pod”) that may be used as a component of a larger pumping system.The reciprocating positive-displacement pump 25 includes a “top” portion(also referred to as the “pumping chamber wall”) 31 and a “bottom”portion (also referred to as the “actuation chamber wall”) 32 that arecoupled together at pod wall 30, for example, by ultrasonic welding orother technique. It should be noted that the terms “top” and “bottom”are relative and are used here for convenience with reference to theorientation shown in FIG. 3. Each of the portions 31 and 32 has a rigidinterior surface that is preferably (although not necessarily)hemispherical, such that the pod has an interior cavity that ispreferably (although not necessarily) spherical.

In the embodiment shown in FIG. 3, the actuation chamber wall 32 is aunitary structure while the pumping chamber wall 31 is formed from twohalves that are coupled together along perimeter 2052, for example, byultrasonic welding or other technique (which facilitates assembly of theintegral valves, discussed below). FIG. 37 shows an exploded view of thethree pump pod wall sections in accordance with an exemplary embodimentof the present invention. FIG. 38A shows a top view of the assembledthree-piece pump pod. FIG. 38B shows a side cross-sectional view of theassembled three-piece pump pod. FIG. 39 shows an exploded view of thepump pod components. FIGS. 37-39 are discussed in greater detail below.Of course, the present invention is in no way limited to the way inwhich the pumping chamber wall 31 and the actuation chamber wall 32 areconstructed or assembled, although ultrasonic welding of the pumpingchamber wall 31 and the actuation chamber wall 32 is considered apreferred embodiment.

Within the reciprocating positive-displacement pump 25, a flexiblemembrane 33 (also referred to as the “pump diaphragm”) is mounted wherethe pumping-chamber wall 31 and the actuation-chamber wall 32 meet(i.e., at the pod wall 30). The pump diaphragm 33 effectively dividesthat interior cavity into a variable-volume pumping chamber (defined bythe rigid interior surface of the pumping chamber wall 31 and a topsurface of the membrane 33) and a complementary variable-volumeactuation chamber (defined by the rigid interior surface of theactuation chamber wall 32 and a bottom side of the membrane 33). The topportion 31 includes a fluid inlet 34 and a fluid outlet 37, both ofwhich are in fluid communication with the pumping chamber. The bottomportion 32 includes a pneumatic interface 38 in fluid communication withthe actuation chamber. As discussed in greater detail below, themembrane 33 can be urged to move back and forth within the cavity byalternately applying negative and positive pneumatic pressure at thepneumatic interface 38. As the membrane 33 reciprocates back and forthin the embodiment shown in FIG. 3, the sum of the volumes of the pumpingand actuation chambers remains constant.

During typical fluid pumping operations, the application of negativepneumatic pressure to the pneumatic interface 38 tends to withdraw themembrane 33 toward the actuation chamber wall 32 so as to expand thepumping chamber and draw fluid into the pumping chamber through theinlet 34, while the application of positive pneumatic pressure tends topush the membrane 33 toward the pumping chamber wall 31 so as tocollapse the pumping chamber and expel fluid in the pumping chamberthrough the outlet 37. During such pumping operations, the interiorsurfaces of the pumping chamber wall 31 and the actuation chamber wall32 limit movement of the membrane 33 as it reciprocates back and forth.In the embodiment shown in FIG. 3, the interior surfaces of the pumpingchamber wall 31 and the actuation chamber wall 32 are rigid, smooth, andhemispherical. In lieu of a rigid actuation-chamber wall 32, analternative rigid limit structure—for example, a portion of a bezel usedfor providing pneumatic pressure and/or a set of ribs—may be used tolimit the movement of the membrane as the pumping chamber approachesmaximum value. Bezels and rib structures are described generally in U.S.patent application Ser. No. 10/697,450 entitled BEZEL ASSEMBLY FORPNEUMATIC CONTROL filed on Oct. 30, 2003 and published as PublicationNo. US 2005/0095154 (Attorney Docket No. 1062/D75) and related PCTApplication No. PCT/US2004/035952 entitled BEZEL ASSEMBLY FOR PNEUMATICCONTROL filed on Oct. 29, 2004 and published as Publication No. WO2005/044435 (Attorney Docket No. 1062/D71 WO), both of which are herebyincorporated herein by reference in their entireties. Thus, the rigidlimit structure—such as the rigid actuation chamber wall 32, a bezel, ora set of ribs—defines the shape of the membrane 33 when the pumpingchamber is at its maximum value. In a preferred embodiment, the membrane33 (when urged against the rigid limit structure) and the rigid interiorsurface of the pumping chamber wall 31 define a sphericalpumping-chamber volume when the pumping chamber volume is at a maximum.

Thus, in the embodiment shown in FIG. 3, movement of the membrane 33 islimited by the pumping-chamber wall 31 and the actuation-chamber wall32. As long as the positive and negative pressurizations providedthrough the pneumatic port 38 are strong enough, the membrane 33 willmove from a position limited by the actuation-chamber wall 32 to aposition limited by the pumping-chamber wall 31. When the membrane isforced against the actuation-chamber wall 32, the membrane and thepumping-chamber wall 31 define the maximum volume of the pumpingchamber. When the membrane is forced against the pumping-chamber wall31, the pumping chamber is at its minimum volume.

In a preferred embodiment, the pumping-chamber wall 31 and theactuation-chamber wall 32 both have a hemispheroid shape so that thepumping chamber will have a spheroid shape when it is at its maximumvolume. More preferably, the pumping-chamber wall 31 and theactuation-chamber wall 32 both have a hemispherical shape so that thepumping chamber will have a spherical shape when it is at its maximumvolume. By using a pumping chamber that attains a spheroid shape—andparticularly a spherical shape—at maximum volume, circulating flow maybe attained throughout the pumping chamber. Such shapes accordingly tendto avoid stagnant pockets of fluid in the pumping chamber. As discussedfurther below, the orientations of the inlet 34 and outlet 37—with eachbeing substantially tangential to the interior surface of the pumpingchamber wall 31—also tend to improve circulation of fluid through thepumping chamber and reduce the likelihood of stagnant pockets of fluidforming. Additionally, compared to other volumetric shapes, thespherical shape (and spheroid shapes in general) tends to create lessshear and turbulence as the fluid circulates into, through, and out ofthe pumping chamber.

1.2. Exemplary Inlet/Outlet Valves

Generally speaking, reciprocating positive-displacement pumps of thetypes just described may include, or may be used in conjunction with,various valves to control fluid flow through the pump. Thus, forexample, the reciprocating positive-displacement pump may include, or beused in conjunction with, an inlet valve and/or an outlet valve. Thevalves may be passive or active. In the exemplary embodiment shown inFIG. 3, the reciprocating positive-displacement pump 25 includes apassive one-way inlet check valve 35 and a passive one-way outlet checkvalve 36. The inlet check valve 35 allows fluid to be drawn into thepumping chamber through the inlet 34 but substantially prevents backflowthrough the inlet 34. The outlet check valve 36 allows fluid to bepumped out of the pumping chamber through the outlet 37 butsubstantially prevents backflow through the outlet 37.

Thus, in an exemplary embodiment using the reciprocatingpositive-displacement pump 25, the membrane 33 is urged back and forthby positive and negative pressurizations of a gas provided through thepneumatic port 38, which connects the actuation chamber to apressure-actuation system. The resulting reciprocating action of themembrane 33 pulls liquid into the pumping chamber from the inlet 34 (theoutlet check valve 36 prevents liquid from being sucked back into thepumping chamber from the outlet 37) and then pushes the liquid out ofpumping chamber through the outlet 37 (the inlet check valve 35 preventsliquid being forced back into the inlet 34).

In alternative embodiments, active valves may be used in lieu of thepassive check valves 35 and 36. The active valves may be actuated by acontroller in such a manner as to direct flow in a desired direction.Such an arrangement would generally permit the controller to cause flowin either direction through the pump pod 25. In a typical system, theflow would normally be in a first direction, e.g., from the inlet to theoutlet. At certain other times, the flow may be directed in the oppositedirection, e.g., from the outlet to the inlet. Such reversal of flow maybe employed, for example, during priming of the pump, to check for anaberrant line condition (e.g., a line occlusion, blockage, disconnect,or leak), or to clear an aberrant line condition (e.g., to try todislodge a blockage).

1.3. Exemplary Pump Inlet/Outlet Orientations

In the embodiment shown in FIG. 3, the inlet 34 and the outlet 37 areoriented so as to direct fluid into and out of the pumping chamber atangles that are substantially tangential to the interior surface of thepumping chamber wall 31. Thus, the fluid flow through the inlet 34 intothe pumping chamber avoids being perpendicular to the membrane 33, evenas the membrane approaches a position where the pumping chamber is atits minimum volume. This orientation of the inlet 34 and the outlet 37tends to reduce the shear forces on the liquid being pumped,particularly when compared to centrifugal pumps, which generally apply agreat deal of stress on the fluid being pumped.

The orientation of the inlet 34 and outlet 37 with respect to each otheralso tends to reduce shear flow and turbulence. When the pumping chamberreaches its maximum volume, the fluid continues circulating through thepumping chamber even as fluid stops flowing through the inlet 34. Thedirection of this circulating flow is a result of the direction of theinlet 34 and the internal flow geometry. Generally speaking, after avery short pause, the membrane 33 will be actuated to start moving toreduce the volume of the pumping chamber and fluid will start flowingthrough the outlet 37. When the fluid enters the pumping chamber, itmoves in a rotating current and stays rotating until exiting the pumpingchamber. The exiting fluid peels off from the outer layer of therotating current in the same direction in which it was rotating. Thespherical shape of the pump pods is particularly advantageous to achievethe desired flow circulation. The orientation of the outlet 37 withrespect to circulating flow within the pumping chamber at the moment ofmaximum pumping chamber volume is such that flow does not have to changedirection sharply when it begins to be urged through the outlet 37. Byavoiding sharp changes in flow direction, shear and turbulence isreduced. Thus, the orientation of the inlet 34 and outlet 37 withrespect to each other and the internal flow geometry reduces shear andturbulence on the liquid being pumped. For example, in FIG. 3, there isonly a small change in direction in a path extending from the inlet 34directly to the outlet 37, but other arrangements will also reduce sharpchanges in direction as the pump pod transitions from a fill stroke toan expel stroke.

Thus, when the fluid being pumped is whole blood, centrifugal pumps(which apply a great deal of stress on the red blood cells) can cause alarge amount of hemolysis and therefore can reduce a patient'shematocrit to the detriment of the patient, whereas pump pods of thetypes described above (which apply low shear forces and turbulence) tendto produce substantially lower hemolysis. Similarly, when the fluidbeing pumped is a surfactant or other fluid prone to foaming, thereduced shear forces and reduced turbulence of the pod pumps tends toreduce foaming.

FIG. 29 is a schematic representation of circulatory fluid flow in thepump pod 25 shown in FIG. 3, in accordance with an exemplary embodimentof the present invention. As fluid enters the pumping chamber throughthe inlet, the orientation of the inlet directs fluid tangentially tothe inside surface of the pumping chamber wall so as to create acirculatory flow. As fluid approaches the outlet, the fluid is alreadyflowing substantially in the direction of the outlet so that the fluidis not required to make any drastic changes in direction when beingpumped from the outlet. The fluid therefore tends to peel off of thecirculatory flow in a laminar fashion to provide reduced shear forces onthe fluid.

Generally speaking, for low shear and/or low turbulence applications, itis desirable for the inlet and outlet to be configured so as to avoidsharp or abrupt changes of fluid direction. It is also generallydesirable for the inlet and outlet (and the pump chamber itself) to befree of flash or burrs. The inlet and/or outlet may include roundededges to help smooth out fluid flow.

1.4. Alternative Pump Configurations

FIG. 20 is a sectional view of an alternative pump pod 2025 such as maybe incorporated into a larger fluid-control cassette, in accordance withan alternative embodiment of the present invention. In this embodiment,the pump pod is formed from three rigid pieces, namely a “top” plate2091, a middle plate 2092, and a “bottom” plate 2093 (it should be notedthat the terms “top” and “bottom” are relative and are used here forconvenience with reference to the orientation shown in FIG. 20). The topand bottom plates 2091 and 2093 may be flat on both sides, while themiddle plate 2092 is provided with channels, indentations and holes todefine the various fluid paths, chambers, and ports. To form the pumppod 2025, the top and bottom plates 2091 and 2093 may include generallyhemispheroid portions that together define a hemispheroid chamber.

A membrane 2109 separates the central cavity of the pump pod into achamber (the pumping chamber) that receives the fluid to be pumped andanother chamber (the actuation chamber) for receiving the control gasthat pneumatically actuates the pump. An inlet 2094 allows fluid toenter the pumping chamber, and an outlet 2095 allows fluid to exit thepumping chamber. The inlet 2094 and the outlet 2095 may be formedbetween middle plate 2092 and the bottom plate 2093. Pneumatic pressureis provided through a pneumatic port 2106 to either force, with positivegas pressure, the membrane 2109 against one wall of pump pod's cavity tominimize the pumping chamber's volume (as shown in FIG. 20), or to draw,with negative gas pressure, the membrane towards the other wall of thepump pod's cavity to maximize the pumping chamber's volume.

The membrane 2109 is provided with a thickened rim 2088, which is heldtightly in a groove 2089 in the middle plate 2092. Thus, the membrane2109 can be placed in and held by the groove 2089 before the top plate2091 is ultrasonically welded to the middle plate 2092, so the membranewill not interfere with the ultrasonic welding of the two platestogether, and so that the membrane does not depend on the two platesbeing ultrasonically welded together in just the right way to be held inplace. Thus, this pump pod should be able to be manufactured easilywithout relying on ultrasonic welding to be done to very tighttolerances.

One or more pump pods 2025 may be incorporated into a single cassette,which may also include one or more valves 2000. FIG. 21 is a sectionalview of a pneumatically controlled valve 2000 that may be used inembodiments of the above-mentioned cassette. A membrane 2090, along withthe middle plate 2092, defines a valving chamber 2097. Pneumaticpressure is provided through a pneumatic port 2096 to either force, withpositive gas pressure, the membrane 2090 against a valve seat 2099 toclose the valve, or to draw, with negative gas pressure, the membraneaway from the valve seat to open the valve. A control gas chamber 2098is defined by the membrane 2090, the top plate 2091, and the middleplate 2092. The middle plate 2092 has an indentation formed on it, intowhich the membrane 2090 is placed so as to form the control gas chamber2098 on one side of the membrane and the valving chamber 2097 on theother side.

The pneumatic port 2096 is defined by a channel formed on the “top”surface of the middle plate 2092, along with the top plate 2091. Byproviding fluid communication between several valving chambers in acassette, valves can be ganged together so that all the valves gangedtogether can be opened or closed at the same time by a single source ofpneumatic pressure. Channels formed on the “bottom” surface of themiddle plate 2092, along with the bottom plate, define the valve inlet2094 and the valve outlet 2095. Holes formed through the middle plate2092 provide communication between the inlet 2094 and the valvingchamber 2097 (through the valve seat 2099) and between the valvingchamber and the outlet 2095.

The membrane 2090 is provided with a thickened rim 2088, which fitstightly in a groove 2089 in the middle plate 2092. Thus, the membrane2090 can be placed in and held by the groove 2088 before the top plate2091 is ultrasonically welded to the middle plate 2092, so the membranewill not interfere with the ultrasonic welding of the two platestogether, and so that the membrane does not depend on the two platesbeing ultrasonically welded together in just the right way to be held inplace. Thus, this valve should be easy to manufacture without relying onultrasonic welding to be done to very tight tolerances. As shown in FIG.21, the top plate 2091 may include additional material extending intocontrol gas chamber 2098 so as to prevent the membrane 2090 from beingurged too much in a direction away from the groove 2089, so as toprevent the membrane's thickened rim 2088 from popping out of the groove2089.

Referring now to FIGS. 30A and 30B, one embodiment of the pod pump 3000is shown. In this embodiment, the pod pump 3000 includes a housing.Referring now to FIG. 30B, the housing includes two portions 3002, 3004.The portions 3002, 3004 are joined and retain a diaphragm 3006.Referring to FIG. 30A, as shown in this embodiment, the housing portions3002, 3004 are joined by screws. However, in alternate embodiments, anyfasteners or fastening method can be used, which include, but are notlimited to: snap together tabs, ultrasonic welding, laser welding orother assembly means known in the art.

Although as shown in the embodiments in FIGS. 30A and 30B, the housingis formed by two portions 3002, 3004, in other embodiments (somedescribed below) the housing is formed from more than two portions. Instill other embodiments, the housing is a single portion.

In various embodiments, the size of the housing may vary. The size mayvary depending on the volume of subject fluid intended to be pumped byeach stroke of the pod pump. Another factor that may influence the sizeis the desired aspect ratio of the pod pump.

Also, in various embodiments, the shape of the housing chamber may vary.Thus, although FIGS. 30A and 30B, as well as many of the additionalfigures in this description describe and show substantially sphericalpod pump housing, the pod pump housing is by no means limited to aspherical shape. Referring now to FIGS. 42A and 42B, an alternate podpump 4200 shape is shown. Thus, although only two shapes are shownherein, in alternate embodiments, the pod pump housing can be any shapedesired.

Referring now to FIGS. 42A and 42B, an alternate embodiment of the podpump is shown. Although in this embodiment, the pod pump is oval shaped,in still other embodiments, the pod pump can be any shape desired. Manyof the embodiments of the pod pumps will include a pump chamber, anactuation chamber, a diaphragm (or movable member), at least oneactuation port and at least one inlet/outlet port. In some embodiments,the pod pump includes an inlet and an outlet port. Various embodimentsare described herein and features described with respect to oneembodiment should be understood to be available for any embodiment, thusthe embodiment features can be mixed and matched, and any embodiment caninclude one or more of the features described herein.

Referring again to FIGS. 30A and 30B the pod pump shown in thisembodiment, is substantially spherical. As shown in this embodiment, thepump housing (which includes the pump chamber and the actuation chamber)is substantially spherical; however, the lip or facade around the pumphousing is not entirely spherical. Thus, the exterior of the housing canbe any shape, and in some embodiments, the exterior of the housing is adifferent shape from the pump housing. However, in some embodiments, theexterior housing is the same shape or substantially the same shape asthe pump housing.

The housing portions 3002, 3004, when joined, form a hollow chamber. Inembodiments where the housing is a single portion, the interior of thehousing is a hollow chamber. Where a diaphragm 3006 is connected orattached to the interior of the housing, the diaphragm 3006 divides theinterior of the housing into two chambers, an actuation chamber 3010 anda pump chamber 3012. In some embodiments, the interior of the housing isdivided into equal volume chambers, however, in other embodiments, thechambers are varying volume chambers.

The diaphragm 3006 may be made of any flexible material having a desireddurability and compatibility with the subject fluid. The diaphragm 3006can be made from any material that may flex in response to liquid or gaspressure or vacuum applied to the actuation chamber 3010. The diaphragmmaterial may also be chosen for particular bio-compatibility,temperature compatibility or compatibility with various subject fluidsthat may be pumped by the diaphragm 3006 or introduced to the chambersto facilitate movement of the diaphragm 3006. In the exemplaryembodiment, the diaphragm 3006 is made from high elongation silicone.However, in other embodiments, the diaphragm 3006 is made from anyelastomer or rubber, including, but not limited to, silicone, urethane,nitrite, EPDM or any other rubber or elastomer.

The shape of the diaphragm 3006 is dependent on multiple variables.These variables include, but are not limited to: the shape of thechamber; the size of the chamber; the subject fluid characteristics; thevolume of subject fluid pumped per stroke; and the means or mode ofattachment of the diaphragm 3006 to the housing. The size of thediaphragm 3006 is dependent on multiple variables. These variablesinclude, but are not limited to: the shape of the chamber; the size ofthe chamber; the subject fluid characteristics; the volume of subjectfluid pumped per stroke; and the means or mode of attachment of thediaphragm 3006 to the housing. Thus, depending on these or othervariables, the shape and size of the diaphragm 3006 may vary in variousembodiments. The diaphragm 3006 can have any thickness. However, in someembodiments, the range of thickness is between 0.002 inches to 0.125inches. Depending on the material used for the diaphragm, the desiredthickness may vary. In one embodiment, high elongation silicone is usedin a thickness ranging from 0.015 inches to 0.050 inches.

In the exemplary embodiment, the diaphragm 3006 is pre-formed to includea substantially dome-shape in at least part of the area of the diaphragm3006. One embodiment of the dome-shaped diaphragm 3006 is shown in FIG.35A as 3514. Again, the dimensions of the dome may vary based on some ormore of the variables described above. However, in other embodiments,the diaphragm 3006 may not include a pre-formed dome shape.

In the exemplary embodiment, the diaphragm 3006 dome is formed usingcompression molding. However, in other embodiments, the dome may beformed by using injection molding.

In alternate embodiments, the diaphragm 3006 is substantially flat untilactuated. In other embodiments, the dome size, width or height may vary.

In various embodiments, the diaphragm 3006 may be held in place byvarious means and methods. In one embodiment, the diaphragm 3006 isclamped between the portions of the housing, and in some of theseembodiments, the rim of the housing may include features to grab thediaphragm 3006. In others of this embodiment, the diaphragm 3006 isclamped to the housing using at least one bolt or another device. Inanother embodiment, the diaphragm 3006 is over-molded with a piece ofplastic and then the plastic is welded or otherwise attached to thehousing. In another embodiment, the diaphragm 3006 is bonded to amid-body portion (not shown, described below with respect to FIGS.33A-34B) and the actuation housing portion. Although some embodimentsfor attachment of the diaphragm 3006 to the housing are described, anymethod or means for attaching the diaphragm 3006 to the housing can beused. The diaphragm 3006, in one alternate embodiment, is attacheddirectly to one portion of the housing at the attachment points 3018.

In the embodiment shown in FIG. 30B, the diaphragm 3006 is held in placein the interior of the housing at attachment points 3018 using one ofthe above described embodiments or another method for attachment. Theattachment points 3018 are areas where the diaphragm 3006 is heldbetween the two portions 3002, 3004 of the housing at the two portions'3002, 3004 meeting point. In some embodiments, the diaphragm 3006 isthicker at the attachment points 3018 than in other areas of thediaphragm 3006. In some embodiments, this thicker area is a gasket, insome embodiments an O-ring, ring or any other shaped gasket. Referringnow to FIG. 35A, an embodiment of the diaphragm 3514 is shown with agasket 3520. In these embodiments, the gasket 3520 is the point thatconnects to the housing.

In some embodiments of the gasket 3520, the gasket 3520 is contiguouswith the diaphragm 3514. However, in other embodiments, the gasket 3520is a separate part of the diaphragm 3514. In some embodiments, thegasket 3520 is made from the same material as the diaphragm 3514.However, in other embodiments, the gasket 3520 is made of a materialdifferent from the diaphragm 3514. In some embodiments, the gasket 3520is formed by over-molding a ring around the diaphragm 3514. The gasket3520 can be any shape ring or seal desired so as to complement the podpump housing embodiment. In some embodiments, the gasket 3520 is acompression type gasket.

The interior of the housing includes at least one port for subject fluid(pump port) and at least one port for actuation fluid (actuation port).Referring to FIG. 30B, the actuation port 3008 and pump port 3014 areshown. Although the embodiment shown in FIG. 30B includes one pump port3014 and one actuation port 3008, in other embodiments (some of whichare described below) the pod pump includes more than one pump portand/or more than one actuation port.

Still referring to FIG. 30B, the location of the pump port 3014 and theactuation port 3008 may also vary in the different embodiments. In theembodiment shown, the pump port 3014 and the actuation port 3008 arelocated on one side of the pod pump 3000. In other embodiments, somewhich are shown and described herein, the pump port and the actuationport may be in various locations on the pod pump, sometimes the sameside, sometimes different side, and in embodiments having more than onepump port and/or more than one actuation port, the locations of all ofthese ports can vary. In most embodiments, however, the actuation port(or, in some embodiments, at least one actuation port) 3008 is in fluidcommunication with the actuation chamber 3010 and the pump port (or, insome embodiments, at least one actuation port) 3014 is in fluidcommunication with the pump chamber 3012.

The actuation port 3008 communicates liquid or gas pressure with aliquid or gas source to add or remove liquid or gas from the actuationchamber 3010. Upon addition or removal of liquid or gas from theactuation chamber 3010 the diaphragm 3006 flexes to increase or decreasethe volume of the pumping chamber 3012. The action of the diaphragm 3006flexing causes the movement of the subject fluid either into or out of apump port 3014. In the embodiments shown in FIG. 30B, both the actuationport 3008 and pumping port 3014 are aligned for attachment to or removalfrom other equipment. However, as discussed above, the ports may beoriented in any manner desired.

Still referring to FIG. 30B, in the embodiment shown, O-rings 3020 arelocated at the actuation port 3008 and pumping port 3014. However, inother embodiments, other means for connecting the pod pump 3000 to otherequipment such as barbed connectors, quick connects, glue, clamps andother fastening means may be used. Referring to FIG. 30A, in oneembodiment, flex tabs 3016 are provided to facilitate the fastening ofthe pod pump 3000 to other equipment, however, in alternate embodiments,additional or alternative locating and fastening features or means maybe used. In still other embodiments, fastening features may not bepresent on the pod pump 3000.

Movement of the diaphragm 3006 causes the volume of the pump chamber3012 and the volume of the actuation chamber 3010 to change. When thevolume of the actuation chamber 3010 decreases, the volume of the pumpchamber 3012 increases. This in turn creates a negative pressure in thepump chamber 3012. The negative pressure causes the subject fluid toenter the pump chamber 3012.

When a positive pressure is present in the actuation chamber 3010,either through air or liquid entering the actuation chamber 3010 throughone or more actuation ports 3008, the volume of the pump chamber 3012decreases, creating a positive pressure in the pump chamber 3012. Thepositive pressure urges the subject fluid out of the pump chamber 3012through one or more pump ports 3014. Although one pump port 3014 isshown, in other embodiments, more than one pump port is included. Insome of these embodiments, one pump port is an inlet port and one pumpport is an outlet port. The location, position and configurations of thepump ports vary and in may vary accordingly to a particular intendedpurpose.

Referring now to FIGS. 31A and 31B, another embodiment of the pod pump3100 is shown. In this embodiment, the housing includes two portions3102, 3104. Referring now to FIG. 31B, a diaphragm 3106 is connected tothe interior chamber of the housing at points 3116. In this embodiment,the diaphragm 3106 is connected to the housing at a position where thetwo portions 3102, 3104 meet. This sandwiches the diaphragm 3106 holdingthe diaphragm 3106.

The diaphragm 3106 divides the interior of the pod pump 3100 housinginto two chambers; an actuation chamber 3108 and a pump chamber 3110. Inthis embodiment the pump chamber 3110 includes with two pump ports 3114,either of which may be an inlet or outlet port when the pump isactuated. Referring again to both FIGS. 31A and 31B, the pod pump 3100includes barbed connectors 3112, which may be used for the attachment oftubing to the pump ports 3114 and actuation port 3118. The duty of eachport is determined by the configuration of other equipment the port isattached to. In this embodiment barbed connectors 3112 are provided forthe attachment of tubing but other attachment methods are possible.

Referring now to FIGS. 32A and 32B, an alternate embodiment of the podpump 3000 similar to the pod pump shown in FIGS. 30A and 30B is shown.However, in this embodiment, an additional component 3202 is included inthe actuating chamber 3108. In some embodiments, an additional component3202 can also be included in the pump chamber 3110, and in otherembodiments, an additional component 3202 can be included in just thepump chamber. The additional component 3202 may serve to limit themotion of the diaphragm 3006, dampen the diaphragm's 3006 travel, filterair or gas entering or leaving the actuation chamber 3108 or dampensound or vibration in the pod pump 3000. In some embodiments, e.g.,where the pod pump 3000 is used in a fluid management system, anadditional component 3202 may be present in both chambers to quicken thetime for equalizing temperature within the chambers. In some of theseembodiments, the additional component(s) 3202 may include a meshplastic, a woven type material, a copper wool, a foam material, or othermaterial, and may create a greater surface area to equilibrate air orother gas. In some embodiments, the additional component(s) 3202 may bepart of a fluid management system (FMS) and may be used to performcertain fluid management system measurements, such as, for example,measuring the volume of subject fluid pumped through the pump chamberduring a stroke of the diaphragm 3006 or detecting air in the pumpingchamber, e.g., using techniques described in U.S. Pat. Nos. 4,808,161;4,826,482; 4,976,162; 5,088,515; and 5,350,357, which are herebyincorporated herein by reference in their entireties. The additionalcomponent 3202 may completely or partially cover the actuation chamberport or may be completely free of the actuation chamber port.

In the preceding figures, various embodiments, characteristics andfeatures of the pod pump are described and shown. The variouscharacteristics can be “mixed-and-matched”, i.e., any one characteristiccan be added to any embodiment of the pod pump. The configurations shownare for example only, and the location of the ports, number of ports,attachment means, size of the housing, sizes of the chamber, etc., mayvary in the different embodiments. The figures and embodiments describedbelow additionally include various embodiments, characteristics andfeatures, all of which also can be “mixed-and-matched” with any of thecharacteristics and features described in any of the embodiments in thisdescription.

Referring to FIGS. 33A and 33B, an alternate embodiment of a pod pump3300 is shown with a pump chamber cover 3302, an actuation chamber cover3304 and a mid plate portion 3306. In this embodiment the mid plate 3306and the actuation chamber cover 3304 retain the diaphragm 3308 and oneor more secondary diaphragms 3310 or 3312. The secondary diaphragms mayact passively or may be actuated by gas, liquid or mechanical forces toserve as active valves to control the flow of fluid through the pumpchamber cover fluid path 3314. In this embodiment of the pod pump 3300,a fluid path 3314 is formed in the pump chamber cover 3302 such thatfluid may flow through the flow path 3314 regardless of the position ofthe diaphragm 3308. In this embodiment as in other embodiments the pumpchamber cover 3302, actuation chamber cover 3304 and mid plate 3306, inone embodiment, are made of plastic but in other embodiments, may bemade from other materials including but not limited to metal or glass.In this embodiment the pump chamber cover 3302, actuation chamber cover3304 and mid plate 3306 may be joined by laser welding or may be joinedby various other methods as deemed appropriate for the chosen componentmaterials and the desired pod pump use. Other joining possibilitiesinclude but are not limited to snap together tabs, press fit, snap fit,solvent bonding, heat welding, electromagnetic welding, resistancewelding, RF welding, screws, bolts, ultrasonic welding, adhesive,clamping by components that neighbor the pump when in use or otherjoining methods commonly used in the art.

Referring now to FIGS. 34A and 34B one embodiment of a pod pump 3400 isshown. In this embodiment inlet and outlet ports are located at oppositeends of the pump chamber 3406 and are interchangeable depending on theconfiguration of the pump or its intended use. The diaphragm 3408 isshown nearly fully extended into the pump chamber 3406. In thisembodiment the inlet and outlet ports 3402 and 3404 may be partially orfully obscured by the diaphragm 3408 when fully actuated by fluidpressure in the actuation chamber 3410. Blocking of the inlet or outletports may serve to limit or switch the flow of subject fluid through thepump chamber 3406 as may be desired in certain applications. In thisembodiment the pumping side of the diaphragm 3408, i.e., the side of thediaphragm 3408 that contacts the subject fluid, is smooth, which mayprovide different flow characteristics with some subject fluids orprovide different contact between the diaphragm 3408 and pump chamber3406 when reduction of flow through the inlet or outlet ports 3402 and3404 is desired when the diaphragm is fully extended into the pumpchamber 3406.

In some embodiments, the diaphragm has a variable cross-sectionalthickness, as shown in FIG. 34B. Thinner, thicker or variable thicknessdiaphragms may be used to accommodate the strength, flexural and otherproperties of the chosen diaphragm materials. Thinner, thicker orvariable diaphragm wall thickness may also be used to manage thediaphragm thereby encouraging it to flex more easily in some areas thanin other areas, thereby aiding in the management of pumping action andflow of subject fluid in the pump chamber 3406. This embodiment thediaphragm 3408 is shown having its thickest cross-sectional area closestto its center. However in other embodiments having a diaphragm 3408 witha varying cross-sectional, the thickest and thinnest areas may be in anylocation on the diaphragm 3408. Thus, for example, the thinnercross-section may be located near the center and the thickercross-sections located closer to the perimeter of the diaphragm 3408.Still other configurations are possible. Referring to FIGS. 35B-E, oneembodiment of a diaphragm is shown having various surface embodiments,these include smooth (FIG. 35 ), rings (FIG. 35E), ribs (FIG. 35D),dimples or dots (FIG. 35C) of variable thickness and or geometry locatedat various locations on the actuation and or pumping side of thediaphragm 3408. In one embodiment of the diaphragm, the diaphragm has atangential slope in at least one section, but in other embodiments, thediaphragm is completely smooth or substantially smooth.

Referring now to FIG. 35A a pictorial exploded view of an exemplaryembodiment of a pod pump 3500 is shown. This figure shows one embodimentof the ports, however, an exemplary embodiment is described below withrespect to FIG. 37. In this embodiment the housing is made of threesections. Two of the portions 3502, 3504 may be joined to form a pumpchamber 3506 (portions 3502, 3504 referred to as “pump chamberportions”) and the third portion 3508 (referred to as the actuationchamber portion) includes an actuation chamber 3512 and an actuationport 3510 to communicate fluid pressure to the actuation chamber 3512.The pump chamber portions 3502, 3504 may be joined together to form apump chamber assembly. This assembly may then be joined with theactuation chamber portion 3508 to form the housing.

The diaphragm 3514 is connected to the interior of the housing. In theexemplary embodiment, the diaphragm 3514 is sandwiched between the pumpchamber 3506 and the actuation chamber 3512. The diaphragm 3514segregates the actuation chamber 3512 from the pump chamber 3506.

In this exemplary embodiment, where the pump chamber 3506 is composed oftwo portions 3502, 3504, where the portions are molded, this design mayallow for minimum flash or burrs. Thus, in this embodiment, the pumpchamber will not have flash in the fluid path thus, presents a gentlepumping environment. This embodiment may be advantageous for use withthose subject fluids vulnerable to shearing, and/or where delicatesubject fluids are pumped, thus flash or burrs should be avoided.

In the exemplary embodiment shown in FIG. 35A, the pump 3500 is shownhaving two ports 3518, 3516. For ease of description, these ports 3518,3516 are called “inlet” and “outlet” ports. However, either port 3518,3516 can serve as an inlet port, likewise, either port can serve as anoutlet port. The pump inlet and outlet ports 3516, 3518 connect to thepump chamber 3506 at edges 3520 and 3522. In one embodiment, the edges3520, 3522 are left sharp and are subject to flash when they are moldedwith retractable cores. However, in the exemplary embodiment, the pumpmay be manufactured without retractable cores and therefore may haveradii on the edges 3520, 3522 thereby eliminating flash or burrs fromthe flow path that may damage delicate or sensitive subject fluids.

Still referring to FIG. 35A, as shown in this exemplary embodiment, thepod pump 3500 includes three housing portions 3502, 3504, 3508 and adiaphragm 3514. Two housing portions 3502, 3504 form a pump chamber 3506portion as well as two ports 3516, 3518. A third portion 3508 forms theactuation chamber 3512. The diaphragm 3514 is attached between the pumpchamber 3506 and actuation chamber 3512 by sandwiching the diaphragm lip3520, which in one embodiment, is an integral O-ring, however, in otherembodiments, can be any other shaped gasket, between the rims 3524 ofthe housing portions. In the embodiment shown in FIG. 35A, the diaphragm3514 includes tangent edges. The tangent edges are present where theshape of the diaphragm 3514 is not a continuous dome, thus, in onesection; the diaphragm is conical shaped as indicated by the tangentedges. Although tangent edges are depicted in this embodiment, inalternate embodiments, the diaphragm can include various surfaces, whichmay include, but are not limited to one or more of the following:dimples, rings, ridges, ribs, smooth, or another variable surface.

As discussed above, the pump chamber 3506 and the ports 3516, 3518 areformed by two housing portions 3502, 3504. These portions 3502, 3504 fittogether as described below with respect to FIGS. 36A-36C.

Referring now to FIGS. 36A and 36B, assembled side and end views of thepump 3500 of FIG. 35 are shown. Here the pump chamber portions 3502 and3504 and the actuation chamber portion 3508 have been joined to concealthe diaphragm 3514, not shown. The components of the pod pump housingmay be joined by various methods including but not limited to snaptogether tabs, press fit, snap fit, solvent bonding, heat welding,electromagnetic welding, resistance welding, RF welding, screws, bolts,ultrasonic welding, adhesive, clamping by components that neighbor thepump when in use or other joining methods commonly used in the art.

In the exemplary embodiment as shown in FIGS. 35A-41B, the pod pump 3500housing includes three portions having features, some specific for theportions to be ultrasonically welded. The design of these three portionsincludes features that allows for the portions to be joined byultrasonic welding, but the resultant pod pump is can pump delicatesubject fluids with minimal, if any, resultant damage to the subjectfluid following ultrasonic welding. A description of the three portionsof the housing and the features for assembly is below. Although theseembodiments are described with respect to ultrasonic welding, it shouldbe understood that these embodiments alternatively may be laser weldedor joined using snap together tabs, press fit, snap fit, solventbonding, heat welding, electromagnetic welding, resistance welding, RFwelding, screws, bolts, adhesive, clamping by components that neighborthe pump when in use or other joining methods commonly used in the art.

Referring now to FIG. 36C an enlarged view of one port is shown. Thiscan be either the inlet or outlet port as shown in FIG. 35A. In thisembodiment the inlet and outlet ports are interchangeable and both havesimilar interior and exterior geometry. However, their locations mayvary.

In this embodiment, portions of the housing 3502, 3504 are joined toform a port 3604. In this embodiment the pump chamber portions 3502,3504 are depicted as being joined by ultrasonic welds at the energydirector 3602. However, in alternate embodiments, other joining methods,as described above, can be used. The zone 3606 where housing portions3502, 3504 are joined is at least partially isolated from the fluid pathof the port 3604 by an area 3608. The area 3608 is formed after joiningthe housing portions 3502, 3504 together. The area 3608, in oneembodiment, increases resistance to flow, thus, the area 3608 creates apath of more resistance than the main flow through the chamber. Thus,the area 3608 is a flow inhibiting area. Thus, the flow of fluid to thezone 3606 where the housing portions meet is decreased. This flowinhibiting area 3608 can be any size desired, however, in the embodimentshown, the flow inhibiting area 3608 is created where the distancebetween the two portions may range from 0.001 inch-0.005 inch and insome embodiments a range of 0.015 inch-0.020 inch. However, the area3608 can be any size desired and may vary depending on a number ofvariables including but not limited to: fluid volume, chamber volume andpumping rate. In many embodiments, the distance between the two portions3502, 3504 creating the area 3608 is a fraction of the size or volume ofthe main flow path. In other embodiments, the area 3608 is any size orvolume desired to present desired resistance to the flow of fluid to thearea 3606.

In alternate embodiments, and in some of these embodiments, depending onthe overall volume of the pod pump, the area 3608 may have a larger orsmaller range. The flow inhibiting area 3608 provides a means where iffluid does flow across the flow inhibiting area 3608 it will experiencemuch greater resistance than fluid flowing through the larger area ofthe port 3604. By virtue of less fluid flowing in the flow inhibitingarea 3608 and reaching the zone 3606 where the housing components arejoined, less fluid will tend to contact any burrs, flash, surfaceirregularities or impurities that may be present in area 3606 where thehousing components are joined. This isolation from flash, burrs, surfaceirregularities or other effects of various joining methods may providefor more gentle and safer transport of delicate of sensitive subjectfluids as may be desired for certain applications.

Rounded edges 3612 on the pump housing portions 3502, 3504 provide,amongst other things, a delicate environment for the subject fluid,liquid or gas flowing through the pump 3500. Although the flowinhibiting area 3608 and rounded edges 3612 are shown in specificlocations in FIG. 36C, these features can be present in any area of thepump desired.

Referring now to FIG. 37 an exemplary embodiment of the pod pump isshown. In this figure, the ports are shown having valves 3712 within.Again, as shown in this figure, the pod pump housing has three portions3702, 3704, 3706. Portion 3702 includes the actuation chamber 3704 andalignment features 3706 for assembly with the other two pump housingportions 3704, 3706. In this embodiment the pump housing portions 3704,3706 include areas where one way valves may be installed 3712. Thehousing portions 3702, 3704, 3706 may be joined by ultrasonic welding,laser welding, snap together features, screws, bolts, adhesive or otherjoining methods commonly used in the art.

The diaphragm 3714 is shown with ribs in this embodiment. However, inalternate embodiments, the diaphragm 3714 may include one or more of thevariable surfaces as described above, or alternatively, may be a smoothsurface. Although each of the various figures herein show one embodimentof the diaphragm, any embodiment of the diaphragm may be used inconjunction with any embodiment of the pod pump.

Referring now to FIGS. 38A and 38B, an alternate embodiment of the podpump 3800 is shown. In various embodiments, the pod pump 3800 isconnected to a system, container or otherwise, where fluid is pumpedfrom and/or into. In some embodiments, the fluid is pumped to/from asystem, container or otherwise via a line or tubing. In one embodiment,the fluid is pumped through flexible tubing. In any case, in theseembodiments, the line or tubing is connected to the inlet and outletports 3814 of the pod pump. However, in alternate embodiments, the fluidcan be pumped through a molded fluid line, or the ports can be directlyconnected to the fluid source, or where the fluid is being pumped.

Still referring to FIGS. 38A and 38B, the housing is a multi portiondesign, similar to the design shown in FIG. 37, including a two portionpump chamber housing 3704, 3706. However, in this embodiment, barbedhose connectors 3802 are shown for the connection of flexible tubing(not shown). Other means of connection to a system may be used in otherembodiments. These means include, but are not limited to, quickconnects, press fit or gluing of tubing directly into the inlet oroutlet ports or other means and methods commonly used in the art.

Referring now to FIG. 38B a section view of the embodiment shown in FIG.38A is shown. In this embodiment valves 3816 are installed in theinterior of the port 3814 portion of the housing portions (as shown as3806, 3804 in FIG. 38A). The valves 3816 control the flow of subjectfluid in and out of the pump chamber 3818 as the diaphragm 3808 isactuated by variations in liquid or gas pressure in the actuationchamber 3810. As shown in this embodiment, the valves 3816 are duck billvalves, however, in other embodiments, the valves 3816 can be anypassive or active valves, including but not limited to, ball checkvalves, flapper valves, volcano valves, umbrella valves, a poppet, acontrolled valve or other types of valves used in the art. In thisembodiment the fluid path 3812 is located near the top of the pumpchamber 3818 and has a portion not inhibited by the diaphragm 3808 evenwhen the diaphragm is fully extended into the pump chamber 3806 byliquid or gas pressure applied to the actuating chamber 3810 via theactuation port 3820.

As shown in this embodiment, the diaphragm 3808 includes rings, however,as described above, the diaphragm 3808 can include dimples, rings,and/or ribs, or any other variation on the surface, or, in someembodiments, no variation on the surface. The varying embodiments of thediaphragm can be used in any of the embodiments of the pod pumps.

Referring now to FIG. 39, an exploded pictorial view of one embodimentof a pod pump 3900 is shown. Valves 3902, in some embodiments, may beinstalled in the inlet and or outlet ports 3904 of the pump housingportions 3906 and 3916. The valves 3902 may any passive or active valve,including but not limited to, duck bill valves, ball check valves,flapper valves, volcano valves, umbrella valves, a poppet, a controlledvalve or other types of valves used in the art to control the flow offluid. A diaphragm 3908 is attached between the pump chamber housingportions 3906 and 3916 and the actuation housing portion 3910. Thediaphragm 3908 is made of any sufficiently flexible and durable materialthat it may flex in response to fluid pressure or vacuum applied to theactuation chamber 3910. The diaphragm 3908 material may also be chosenfor particular bio-compatible, temperature compatibility orcompatibility with various gases or liquids that may be introduced tothe pump or actuation chambers.

The diaphragm 3908 may have a ring of thick material 3912 near its outerdiameter to be located or fastened in mating features of the pod pumphousing components 3906, 3916 and 3910. The moveable portion of thediaphragm 3908 includes two surfaces, for purposes of description; thesewill be referred to an exterior surface and an interior surface. Theexterior surface is the pump chamber surface and the interior surface isthe actuation chamber surface. Either surface of the movable portion ofthe diaphragm may be of uniform or variable thickness, and both surfacesdo not have to be the same. Various embodiments of the surface are shownin FIGS. 35B-E. Either or both surfaces may be smooth or include one ormore features including but not limited to dimples, dots, rings, ribs,grooves or bars that stand above or below surrounding surfaces. In thisembodiment, an arrangement of dots 3914 are shown on the exteriorsurface of the diaphragm.

The surface features, or lack thereof, may serve a number of variousfunctions. One of these may be to provide space for fluid to passthrough the pump chamber. Another may be to aid in the diaphragm sealingagainst the pump chamber housing for applications where it is desirableto prevent the flow of fluid through the pump chamber when the diaphragmis pressed against the pump chamber housing by liquid or gas pressure inthe actuation chamber. Some diaphragm surfaces may provide one or moreof these features, or provide another function or feature.

Geometry on the exterior or interior surface of the diaphragm may alsoserve to cushion the movement of the diaphragm at either end of thediaphragm stroke. When geometry on the diaphragm contacts the pump oractuation chamber walls those features will stop moving but thediaphragm material between the features may continue to move to allowthe fluid that is being pumped to be gently accelerated or deceleratedas it enters or leaves the pump chamber.

Referring now to FIG. 40A, a pictorial view of portions 3906 and 3916 ofthe multi portion pump shown in FIG. 39 is shown. For illustrationpurposes only, the pump housing portions 3906 and 3916 are shownoriented base to base to illustrate the relationship of the alignmentand joining features that may be used in the pump portion of amulti-part pod pump housing. The portions 3906 and 3916 align and jointogether in two locations in this exemplary embodiment. However, inother embodiments, these features may vary, and the location of thejoining of the two portions may vary. For purposes of description, oneof the alignment and joining features will be described with respect toFIG. 40B, however, it should be understood, that although one isdescribed, the details can apply to both.

Referring now to FIG. 40B, a close up pictorial view of one area of FIG.40A is shown. Pump housing portion 3916 has an alignment feature 4002that may align with a complimentary alignment groove 4004 on housingportion 3906. In this embodiment the aligning feature 4002 includes anenergy director 4006 so the housing portions 3906 and 3916 may be joinedby ultrasonic welding. In this embodiment the energy director is locatedin line with a relieved area 4008 in the base of the pump housing 3916.The relieved area 4008 may accommodate the outer ring of a diaphragm(not shown), in embodiments where the diaphragm includes an outer ring.

The relieved area 4008 is continued in pump housing portion 3906 but isonly visible as the edge 4010. In this embodiment where ultrasonicwelding is used, flash from the energy director 4006 may attempt to flowbeyond the edge 4010 upon assembly. By virtue of the energy director4006 being in line with the outer ring of the diaphragm (not shown) anyflash will be adjacent the outer ring of the diaphragm which flexes toseal despite the presence of flash on the diaphragm outer ring sealingsurface. When alternate joining methods such as, but not limited to,laser welding, adhesives, screws or other fasteners are used, the energydirector 4006 may be excluded and the geometry of the alignment features4002 and 4004 may vary form the embodiment shown. In the embodiment anadditional aligning feature 4012 and energy director 4014 are present toorient the pump housing components 3906 and 3916 such that they arejoined down to their base where they will be joined to an actuationhousing (not shown) as shown in earlier and subsequent figures.

Referring now to FIG. 41A, a pictorial view of a partially assembled podpump 4100 is shown. For illustration purposes, only one portion of thepump housing 3916, a portion of a possible embodiment of a diaphragm4102 and a portion of an actuator housing 4104 are shown.

Referring now to FIG. 41B, a close up pictorial view of one area of FIG.41A is shown. In this embodiment of the actuator housing 4104, twoenergy directors 4106 and 4108 are shown for joining by ultrasonicwelding although other joining methods are possible. In this embodimentenergy director 4108 is in line with energy director 4014 on pumphousing portion 3916. Aligning the energy directors as shown in thisembodiment ensures that flash from one weld is consumed by the otherultrasonic weld thereby creating a reliable seal between all threehousing portions, one housing portion is excluded from this figure forclarity.

Still referring to FIGS. 41A and 41B, the alignment of energy director4006 with the outer portion of the diaphragm 4102 is shown. Aligningenergy director 4006 with the diaphragm 4102 in this way allows anyflash resulting from an ultrasonic weld in the area of energy director4006 to be sealed by the flexible material of the diaphragm 4102. Thepod pump housing can be made from any material including any plastic,metal, wood or a combination thereof. In one exemplary embodiment, thepod pump housing is made from medical grade polycarbonate. In anotherexemplary embodiment, the pod pump housing is made from polysulfone. Asdescribed in more detail in the description, the compatibility of thematerials selected to the subject fluid may be one factor in someembodiments.

Referring now to FIGS. 42A-42D, an alternate shape embodiment of the podpump 4200 is shown. The shape embodiments shown herein are meant forillustration and description purposes only. In alternate embodiments, itshould be understood that the pod pump can be any shape desired.

The pod pump housing can be manufactured using any one of a number ofmethods of manufacturing, including but not limited to injectionmolding, compression molding, casting, thermoforming or machining. Insome embodiments, for example, where the housing is machined, thehousing can be fused together using mechanical fasteners or heat fused.

The wall thickness of the pod pump housing may vary between embodiments.A myriad of variables may contribute to wall thickness selection. Theseinclude, but are not limited to, the housing material used, pressure atwhich the fluid will be pumped; size of the chambers; overall size ofthe pod pump, strength needed in response to the materials using,durability, assembly method, the device in which the pod pump may beworking in conjunction with, cost and manufacturing time. In someembodiments, the pod pump wall thickness is variable.

The wall thickness, in the various embodiments, can range from 0.005 toany thickness. The term “any thickness” is used because in someembodiments, the pod pump can be integrated into a device or machine.Thus, the wall of the pod pump may be the same thickness as the overallmachine. Thus, in some cases, the wall thickness is quite large. In theexemplary embodiment described herein, the wall thickness ranges from0.04 inch to 0.1 inch. In another embodiment, the wall thickness rangesfrom 0.06 inch to 0.08 inch.

The material selection and method of manufacture of the variousembodiments of the pod pump may depend on a number of variables. Someinclude durability, cost, pressure from the fluid, performance, and manyothers. In some embodiments, the pod pump housing and diaphragm isintended to last months or years. In other embodiments, the pod pump isintended to be a one-use disposable. In still other embodiments, the podpump is intended to last any number of hours, days, weeks or years. Insome embodiments, even where the pod pump is a one-use disposable, thepod pump is designed to pump for a much longer period of time, forexample, days, weeks, months or years.

In one embodiment of the disposable, the housing is made from a thinfilm made of a material which includes, but is not limited to PETE,PETG, and PET. In these embodiments, the housing may be thermoformed,for example, vacuum or pressure formed, and the diaphragm is formed froma thin plastic film that can be heat sealed to the housing. In someembodiments, the housing is a multi-layer film. This embodiment isconducive to bonding the housing to another component.

The pod pump can be incorporated and/or integrated into another device,machine, container, or other, or act in conjunction with another device,machine, container or other. In some embodiments, a single pod pump isused. However, in other embodiments, two or more pod pumps are used. Insome embodiments, the pod pump is incorporated into a device which isthen integrated or attached to a machine, device, container or other.One example of this embodiment is a cassette having integrated podpumps, fluid paths, fluid ports, actuation ports and actuation fluidpaths. Two embodiments of a cassette are described with respect to FIGS.43A-43C and 44A-44B. Many additional embodiments will be understood. Forpurposes of description, an exemplary embodiment and an alternateembodiment will be described. However, these are only exemplary andother embodiments, with greater or less than two pod pumps, usingdifferent valves, various flow paths and incorporating additionalcontainers or other devices, are understood.

Referring now to FIGS. 43A-43C,one embodiment of a pod pump cassette4300 is shown. Referring now to FIG. 43A, this embodiment of the podpump cassette includes two pod pumps 4310. The pod pumps 4310 can be anypod pump embodiment, but in this exemplary embodiment, the pod pumps4310 are similar to the pod pump shown in FIGS. 33A-33B. The cassette4300 includes three plates, an actuation plate 4320, a mid plate 4330and a pump chamber plate 4340.

The actuation plate 4320 includes, for each pod pump 4310, a pod pumpactuation chamber housing 4312 portion and two valves actuation housing4314 portions. The valve actuation housing 4314 includes a valveactuation port 4316. In addition to pod pumps, the cassette 4300, insome embodiments, may contain additional ports and/or containers forvarious fluids to be pumped to and from.

The mid plate 4330 includes, for each pod pump, a pump diaphragm 4332and two valve diaphragms 4334. In the embodiment shown, the valves arevolcano or active valves actuated by a diaphragm 4334 which is actuatedby a fluid, which in this embodiment is pneumatic air. Also shown onthis embodiment of the cassette 4300 are additional diaphragms in themid plate 4330. These are for embodiments that may contain additionalcontainer for various fluids to be pumped to and from.

Referring now to the pump plate 4340, each pod pump 4310 includes a pumpchamber housing 4342 which includes an integral fluid path 4344. Thepump chamber housing 4342 is in fluid connection with an exterior fluidpath 4346. In this exemplary embodiment, the three plates 4320, 4330,4340 are laser welded together. However, in other embodiments, variousmodes of attachment, some of which are described above, may be used.

Referring now to FIG. 43B, a cross sectional view of the cassette 4300is shown. The volcano valves are shown including the valve diaphragms4334, the valves actuation housing 4314 portions and the exterior fluidline 4346. The valves are actuated by pneumatic air through actuationports 4318.

Referring now to FIG. 43C, in some embodiments, an air filter 4350 andan additional fluid line 4352 may be included in the cassette.

An alternate embodiment of the cassette is shown in FIGS. 44A and 44B.Referring now to FIG. 44A, the cassette 4400 includes greater than threeportions. The portions include a mid plate 4410 with multiple covers4412-4416 laser welded onto the mid plate. These multiple covers4412-4416 are used rather than the pump plate shown in FIG. 43A as 4340.Referring now to FIG. 44B, the mid plate 4410 again is shown. However,in this embodiment, multiple covers 4442-4444 are used rather than ansingle actuation plate as shown in FIG. 43A as 4320. As shown in FIGS.44A-44C, this is one embodiment, however, in other embodiments, thenumber of multiple covers may vary.

1.5. Exemplary Embodiments Incorporating Multiple Pump Pods

It should also be noted that pumping systems may employ multiple pumppods for pumping fluid. Pump pods may be employed individually, in whichcase the pump pods may be individually controlled, or pump pods may beinterconnected in various ways, such as, for example, interconnectingthe inlets of multiple pump pods in order to draw fluid from a commonsource, interconnecting the outlets of multiple pump pods in order topump fluid to a common destination, and/or interconnecting the pneumaticports of multiple pump pods in order to control the pump pods through acommon pneumatic interface. In various embodiments, multiple pump podsmay be operated out-of-phase (i.e., one pumping chamber is emptyingwhile the other is filling) in order to provide a substantiallycontinuous flow, in-phase in order to provide a pulsatile flow, or inother ways. For in-phase operation, a single pneumatic interface may beprovided for multiple pump pods so that the base station can operate thepump pods simultaneously. Similarly, a single pneumatic interface may beprovided for multiple valves so that the base station can operate thevalves simultaneously.

In the embodiments shown in FIGS. 2 and 48, two individualself-contained pump pods 25 a and 25 b of the type shown in FIG. 3 areincluded in a disposable system. In this embodiment, each of the pumppods 25 a and 25 b has its own pneumatic port 38, so the pump pods 25 aand 25 b can be controlled separately.

In the embodiment shown in FIGS. 5A and 5B, two pump pods 25 a and 25 bare incorporated into larger assembly 2004 such that the inlets of twopump pods 25 a and 25 b are connected to a common inlet line 54 and theoutlets of both pump pods 25 a and 25 b are connected to a common outletline 57. FIG. 5B shows the pneumatic ports 38 of the pump pods 25 a and25 b. The inlets 34 and outlets 37 of the pump pods 25 a and 25 b arearranged to direct the flows into and out of the pumping chambers atangles that are substantially tangential with the rigid pumping-chamberwalls 31 of each pump pod, in order to—as discussed above—reduce shearforce and turbulence on the fluid and to improve circulation through thepumping chambers. In this embodiment, the pump pods 25 a and 25 b havepurge ports 55, which allow air to be purged from the system, forexample, during priming. Also in this embodiment, the common inlet line54 is fitted with a number of luer ports 2001 (e.g., to permitattachment of additional fluid sources, such as medical solutions,chemical solutions, dilutants, etc.) and is also fitted with athermocouple 2002 (e.g., to allow for monitoring the temperature of thefluid entering the pump pods 25 a and 25 b). Also in this embodiment,the assembly 2004 includes two flow-through ports 2003 having tubeconnections on the top side (shown in FIG. 5A) and o-ring connections onthe bottom side (shown in FIG. 5B). The flow-through ports 2003 can beused to facilitate installation or use of the assembly 2004 with a basestation, for example, by allowing all pneumatic and fluidic connectionsto be made from the bottom of the assembly 2004, in which case the inletline 54 may be pre-connected via tubing to one of the flow-through ports2003 and the outlet line 57 may be pre-connected via tubing to the otherflow-through port 2003.

In the embodiment shown in FIGS. 22A and 22B, two pump pods 2025 a and2025 b of the type shown in FIG. 20 and a number of valves 2000 a-2000 dof the type shown in FIG. 21 are incorporated in a pump cassette 2015along with various fluid paths and other components. The pump cassette2015 includes a common inlet 2005 in fluid communication with pump pod2025 a via fluid paths 2007 and 2009 and with pump pod 2025 b via fluidpaths 2008 and 2010. The pump cassette 2015 also includes a commonoutlet 2006 in fluid communication with pump pod 2025 a via fluid paths2011 and 2013 and with pump pod 2025 b via fluid paths 2012 and 2014.Thus, pump pods 2025 a and 2025 b draw fluid from the common inlet 2005and pump fluid to the common outlet 2006. That being said, valve 2000 ais used to control fluid flow at the intersection of fluid paths 2008and 2010 (i.e., at the inlet to pump pod 2025 b); valve 2000 b is usedto control fluid flow at the intersection of fluid paths 2007 and 2009(i.e., at the inlet to pump pod 2025 a); valve 2000 c is used to controlfluid flow at the intersection of fluid paths 2011 and 2013 (i.e., atthe outlet of pump pod 2025 a); and valve 2000 d is used to controlfluid flow at the intersection of fluid paths 2012 and 2014 (i.e., atthe outlet of pump pod 2025 b). Each of the pump pods 2025 a and 2025 bhas its own pneumatic interface 2106 a and 2106 b, respectively. Also,each of the valves 2000 a-2000 d has its own pneumatic interface 2096a-2096 d, respectively. Thus, each of pump pods and each of the valvescan be independently controlled by a base station.

FIG. 23 is a schematic representation of dual-housing arrangement 2016according to another embodiment of the invention. This arrangement maybe advantageously used with disposable cassettes that include manypneumatically actuated pumps and/or valves. If the number ofpneumatically actuated pumps and/or valves in a cassette is largeenough, the cassette containing these pumps and valves can become solarge—and the pressures involved can become so great—that it may becomedifficult to properly seal and position all of the pumps and valves.This difficulty may be alleviated by using two different housings. Thevalves and pumps (such as pump pods 2042) are placed in a main housing2041, from which connecting tubes 2045 lead from pneumatic ports 2044.The main housing 2041 also has inlet and outlet tubes 2043, which allowliquid to flow into and out of the main housing. The connecting tubes2045 provide pneumatic communication between valves and pumps in themain housing 2041 and a smaller, secondary tube-support housing 2046,which is provided with a pneumatic interface 2047 for each of the tubes.The proper positioning and sealing of all the pneumatic interfaces 2047against receptacles in the base unit can be accomplished more easilywith the smaller tube-support housing 2046 than it would be if thepneumatic actuation was applied to the larger main housing directly.

1.6. Alternative Chamber Configurations and Stroke Sizes

It should be noted that pump pods of the types described above can beconfigured with different chamber configurations and/or different strokesizes. Thus, for example, pump pods having different pump volumes may beprovided. Furthermore, pump pods having different pump volumes may beprovided with a standardized pneumatic port configuration (and perhapsstandardized actuation chamber wall configuration) so that pump podshaving different volumes may be easily swapped into and out of a commonpumping system or apparatus (e.g., a base unit) having a correspondingstandardized pneumatic port interface. For example, the base unit may beable to receive lower-volume pump pods for pediatric use and receivehigher-volume pump pods for adult use. The pneumatic ports arepreferably adapted to be quickly and easily connected to—anddisconnected from—the pneumatic actuation system of the base unit. Incertain embodiments, the pump pods may be considered to be disposableand may be provided individually or as part of a larger disposablesystem.

Thus, for example, in the embodiments shown in FIGS. 2 and 48,disposable systems (specifically for use in a heat-exchange system, asdiscussed more fully below) include two self-contained pump pods 25 aand 25 b. Different versions of such disposable systems having pump podsof different pump volumes could be provided for different applications(e.g., one version with smaller pump volumes for children, anotherversion with larger pump volumes for adults). Similarly, in theembodiment shown in FIGS. 5A and 5B, different versions of the assembly2004 having pump pods of different pump volumes could be provided, andin the embodiment shown in FIGS. 22A and 22B, different versions of thecassette 2015 having pump pods of different pump volumes could beprovided. Similarly, in the embodiment shown in FIG. 23, differentversions of the main housing 2041 having pump pods of different pumpvolumes could be provided for use with a common secondary tube-supporthousing 2046.

It should be noted that the pumping chamber wall may be molded, formed,produced, or otherwise configured with various features facilitateintake, circulation, and/or delivery of the fluid. For example, theinside wall of the pumping chamber may include certain features ormaterials to help induce circulatory flow, induce smooth/laminar flow,reduce boundary layer effects, or even produce turbulence (e.g., tofacilitate mixing of materials or prevent coagulation within the pumpingchamber).

1.7. Exemplary Diaphragm Configurations

In certain embodiments, the pump pod diaphragm may be provided withsmall raised bumps, grooves, or other structures, particularly on theside of the membrane facing the pumping chamber. FIGS. 46A and 46B showan exemplary membrane 33 having raised bumps 39, in accordance with anexemplary embodiment of the present invention. Such raised bumps 39 orother raised structures prevent pockets of fluid from being caught awayfrom the inlet and outlet, specifically by keeping the membrane spacedaway from the rigid pumping chamber wall even when the pumping chambervolume is at a minimum. This spacing keeps flow passages open for bloodto flow from the periphery of the pumping chamber to the outlets. In theexemplary embodiment shown in FIGS. 46A and 46B, the bumps 39 arelocated on a portion of the membrane spaced away from the edge of themembrane such that the membrane lacks bumps in the area near the edge ofthe membrane. Generally speaking, such a configuration allows theportion of the membrane around the edge to contact the pumping chamberwall, which tends to force fluid from the edge toward the outlet.

In addition to, or in lieu of, bumps or other raised structures on themembrane, the pump chamber wall may include spacers or conduits to allowfor fluid flow as the pumping chamber approaches and reaches its minimumvolume.

The membrane may be made from any of a wide variety of flexiblematerials, but is preferably made of a high-elongation silicone orsimilar material in order to maintain smooth pumping of the membrane andto reduce the tendency of membrane to “snap hard” into itsminimum-pumping-chamber-volume position. By reducing hard snapping,sharp localized spikes of force on the fluid are reduced. Such hardsnapping could cause disruptions in the fluid rotation in the chamberand could result in excessive shear forces and turbulence, which, thecase of blood pumping, could cause hemolysis, and in the case ofsurfactant pumping, could result in foaming. Alternatively, the membranemay be made of a variety of thermoplastic elastomers or rubbers. Also,the membrane may be provided with dimples or grooves to make themembrane more flexible.

It should be noted that the membrane may be molded, formed, produced, orotherwise configured so as to bias reciprocation of the membrane in apredetermined pattern or manner. For example, the membrane may be formedwith portions of having different thickness or stiffness so that certainportions move more freely than others (e.g., a portion of the membraneproximate to the pump inlet may be configured to be more flexible than aportion of the membrane proximate to the pump outlet so that the inletside of membrane retreats more quickly during the draw stroke andcollapses more quickly during the delivery stroke, which couldfacilitate filling and emptying of the pumping chamber in someembodiments).

2. Exemplary Pump Control Systems 2.1. Pressure Actuation System

FIG. 4 is a schematic showing an embodiment of a pressure actuationsystem 40 that may be used to actuate a pump pod, such as the pump pod25 shown in FIG. 3, in accordance with an exemplary embodiment of thepresent invention. The pressure actuation system 40 is capable ofintermittently or alternately providing positive and negativepressurizations to the gas in the actuation chamber 42 of the pump pod25. The pump pod 25—including the flexible membrane 33, the inlet 34,the outlet 37, the pneumatic port 38, the pumping chamber 41, theactuation chamber 42, and possibly including an inlet check valve 35 andan outlet check valve 36 or other valves—may be part of a largerdisposable system. The pneumatic actuation system 40—including anactuation-chamber pressure transducer 44, a positive-supply valve 47, anegative-supply valve 48, a positive-pressure gas reservoir 51, anegative-pressure gas reservoir 52, a positive-pressure-reservoirpressure transducer 45, a negative-pressure-reservoir pressuretransducer 46, as well as an electronic controller 49 including a userinterface console (such as a touch-panel screen)—may be part of a baseunit.

The positive-pressure reservoir 51 provides to the actuation chamber 42the positive pressurization of a control gas to urge the membrane 33towards a position where the pumping chamber 41 is at its minimum volume(i.e., the position where the membrane is against the rigidpumping-chamber wall 31). The negative-pressure reservoir 52 provides tothe actuation chamber 42 the negative pressurization of the control gasto urge the membrane 33 in the opposite direction, towards a positionwhere the pumping chamber 41 is at its maximum volume (i.e., theposition where the membrane is against the rigid actuation-chamber wall32).

A valving mechanism is used to control fluid communication between eachof these reservoirs 51, 52 and the actuation chamber 42. In FIG. 4, aseparate valve is used for each of the reservoirs; a positive-supplyvalve 47 controls fluid communication between the positive-pressurereservoir 51 and the actuation chamber 42, and a negative-supply valve48 controls fluid communication between the negative-pressure reservoir52 and the actuation chamber 42. These two valves 47, 48 are controlledby the controller 49. Alternatively, a single three-way valve may beused in lieu of the two separate valves 47, 48. The valves 47, 48 may bebinary on-off valves or variable-restriction valves.

The controller 49 also receives pressure information from the threepressure transducers shown in FIG. 4: an actuation-chamber pressuretransducer 44, a positive-pressure-reservoir pressure transducer 45, anda negative-pressure-reservoir pressure transducer 46. As their namessuggest, these transducers respectively measure the pressure in theactuation chamber 42, the positive-pressure reservoir 51, and thenegative-pressure reservoir 52. The actuation-chamber-pressuretransducer is located in the base unit but is in fluid communicationwith the actuation chamber 42 through the pump pod's pneumatic port 38.The controller 49 monitors the pressure in the two reservoirs 51, 52 toensure they are properly pressurized (either positively or negatively).In one exemplary embodiment, the positive-pressure reservoir 51 may bemaintained at around 750 mmHG, while the negative-pressure reservoir 52may be maintained at around −450 mmHG.

A compressor-type pump or pumps (not shown) may be used to maintain thedesired pressures in these reservoirs 51, 52. For example, twoindependent compressors may be used to respectively service thereservoirs 51, 52. Pressure in the reservoirs 51, 52 may be managedusing a simple bang-bang control technique in which the compressorservicing the positive-pressure reservoir 51 is turned on if thepressure in the reservoir 51 falls below a predetermined threshold andthe compressor servicing the negative-pressure reservoir 52 is turned onif the pressure in the reservoir 52 is above a predetermined threshold.The amount of hysteresis may be the same for both reservoirs or may bedifferent. Tighter control of the pressure in the reservoirs can beachieved by reducing the size of the hysteresis band, although this willgenerally result in higher cycling frequencies of the compressors. Ifvery tight control of the reservoir pressures is required or otherwisedesirable for a particular application, the bang-bang technique could bereplaced with a PID control technique and could use PWM signals on thecompressors.

The pressure provided by the positive-pressure reservoir 51 ispreferably strong enough—under normal conditions—to urge the membrane 33all the way against the rigid pumping-chamber wall 31. Similarly, thenegative pressure (i.e., the vacuum) provided by the negative-pressurereservoir 52 is preferably strong enough—under normal conditions—to urgethe membrane all the way against the actuation-chamber wall 32. In afurther preferred embodiment, however, these positive and negativepressures provided by the reservoirs 51, 52 are within safe enoughlimits that even with either the positive-supply valve 47 or thenegative-supply valve 48 open all the way, the positive or negativepressure applied against the membrane 33 is not so strong as to damagethe pump pod or create unsafe fluid pressures (e.g., that may harm apatient receiving pumped blood or other fluid).

It will be appreciated that other types of actuation systems may be usedto move the membrane back and forth instead of the two-reservoirpneumatic actuation system shown in FIG. 4, although a two-reservoirpneumatic actuation system is generally preferred. For example,alternative pneumatic actuation systems may include either a singlepositive-pressure reservoir or a single negative-pressure reservoiralong with a single supply valve and a single tank pressure sensor,particularly in combination with a resilient diaphragm. Such pneumaticactuation systems may intermittently provide either a positive gaspressure or a negative gas pressure to the actuation chamber of the pumppod. In embodiments having a single positive-pressure reservoir, thepump may be operated by intermittently providing positive gas pressureto the actuation chamber, causing the diaphragm to move toward thepumping chamber wall and expel the contents of the pumping chamber, andreleasing the gas pressure, causing the diaphragm to return to itsrelaxed position and draw fluid into the pumping chamber. In embodimentshaving a single negative-pressure reservoir, the pump may be operated byintermittently providing negative gas pressure to the actuation chamber,causing the diaphragm to move toward the actuation chamber wall and drawfluid into the pumping chamber, and releasing the gas pressure, causingthe diaphragm to return to its relaxed position and expel fluid from thepumping chamber.

2.2. Alternative Embodiments Using Active Inlet/Outlet Valves

As discussed above, active valves may be used instead of passive checkvalves at the pump pod inlet and output. Active valves would allow forgreater control and flexibility (generally at the expense of addedcomplexity and cost). Among other things, active valves would allow forreversal of fluid flow, which could be used, for example, to facilitatepriming, air purging, and/or detection and mitigation of certainconditions (e.g., occlusion, blockage, leakage, line disconnect). Withregard to detection of a line disconnect, a reversal of flow may causeair to be drawn into the pumping chamber through the outlet if theoutlet line is disconnected. Such air flow could be detected using anyof a variety of techniques, including the amount of work needed to movethe pump diaphragm. If the line is safely connected, some amount of workwould normally be necessary to reverse flow and draw fluid in throughthe outlet, whereas if the return line has been disconnected, much lesswork would generally be necessary to reverse flow, since the pump wouldbe drawing air into the return line. If upon reversing flow, thecontroller detects an aberrant flow condition, the controller wouldpreferably cause the system to stop pumping blood from the patient.

During normal pump operations, the active valves generally would beoperated as follows. During a fill stroke, when fluid is drawn into thepumping chamber, the controller 49 would typically open the inlet valveand close the outlet valve so as to allow fluid to enter the pumpingchamber through the inlet but prevent fluid from being drawn back infrom the outlet. During a delivery stroke when fluid is pumped out ofthe pumping chamber (e.g., after the pumping chamber is full or at otherappropriate times), the controller 49 would generally close the inletvalve and open the outlet valve so as to allow fluid to be pumped out ofthe outlet but prevent fluid from being pumped back through the inlet.Between strokes, the controller 49 may cause both the inlet valve andthe outlet valve to be closed for some time interval.

It should be noted that for embodiments in which pneumatically actuatedinlet and outlet valves (e.g., binary on-off valves either integral tothe pump pod or external to the pump pod) are used in place of passiveinlet and outlet check valves, such valves may be coupled to thepositive and/or negative pressure reservoirs 51, 52 through appropriatesupply valves actuated by the controller 49.

The use of active inlet and outlet valves can facilitate detection ofair in the pumping chamber. For example, following a full draw stroke tobring the pumping chamber to its maximum volume, positive pressure canbe applied to the actuation chamber and the rate at which the pressurein the actuation chamber (or the pumping chamber) increases can bemonitored. If the pumping chamber is full of air, then the pressureshould increase more gradually, as the air in the pumping chamber willallow the diaphragm to move more readily. If, however, the pumpingchamber is full of liquid, then the pressure should increase morerapidly because the pump diaphragm will be held more firmly by theuncompressible liquid.

2.3. Pump Operation

During normal pumping operations, the controller 49 typically monitorsthe pressure information from the actuation-chamber-pressure transducer44 and, based on this information, controls the valving mechanism(valves 47, 48) to urge the membrane 33 all the way to itsminimum-pumping-chamber-volume position and then after this position isreached to pull the membrane 33 all the way back to itsmaximum-pumping-chamber-volume position. In this embodiment, volume maybe measured by counting full strokes of fluid delivery (e.g.,volume=number of full strokes x pumping chamber volume).

In typical embodiments of the invention, the controller may be able todetect the end of a stroke, i.e., when the membrane reaches one of therigid pumping-chamber or actuation-chamber walls. Referring to FIG. 4,an expel stroke is started by opening positive-supply valve 47, therebyresulting in positive pressure being exerted against the membrane 33.Preferably, the positive-supply valve 47 is cycled on and off (dithered)to create a ripple in the actuation chamber's pressure as long as themembrane 33 is moving. When the membrane 33 reaches the pumping-chamberwall 31 the pressure ripple stops. The controller 49, receiving pressureinformation from actuation-chamber-pressure transducer 44, monitors thispressure ripple and detects the end of stroke when this pressure ripplestops.

When the controller 49 detects the end of the expel stroke, thecontroller closes positive-supply valve 47 and dithers thenegative-supply valve 48, thereby causing a vacuum to be applied to themembrane 33. The same process followed in the expel stroke is repeatedfor the fill stroke. The controller determines the time to complete eachstroke and uses that information to calculate flow rate. The flow rateinformation is then used to set the commands for pressure and valvingfor the next stroke.

The controller 49 sets the flow rate using a timed sequence ofalternately applying positive pressure and vacuum to the membrane 33. Apositive pressure will be applied for a determined time interval toachieve a desired delivery (i.e., expelling) flow rate. When this timeinterval has expired, a vacuum is applied to achieve a fill flow rate.This control of time intervals can be an open-loop system withoutfeedback on flow rate; thus, there can be delays between the end of onestroke and the start of another. Such an open-loop time-based system maybe used when closed-loop systems based on flow-rate will not operateproperly, such as during priming when there is a mixture of liquid andair in the pump pods.

As mentioned above, a stroke is preferably effected by delivering asequence of pressure pulses (forming a pressure ripple) to the membrane33. The speed of a stroke can be adjusted by changing how frequently asupply valve is opened and/or by changing how long it is opened eachtime it is opened. A pressure pulse involves opening the valve betweenthe actuation chamber and the reservoir for a fixed time and thenclosing it for the rest of the pulse period. The total length of apressure pulse is 1/(pulse pumping frequency). In one embodiment, thepulse pumping frequency increases from 2 Hz to 16 Hz as the controller'spumping command increases from 0 to 100%. The minimum frequency of 2 Hzis intended to ensure a minimum flow rate is met when there is water inthe system. A maximum frequency of 16 Hz is intended to correspond tothe minimum time required for the valve to be at a 50% duty cycle. Thepumping algorithm preferably divides a stroke into two periods, theinitial pumping period and the end-of-stroke period. During the initialpumping period, the valve open time of the pressure pulse is preferably166 ms (100% duty cycle at 16 Hz). Thus, with a maximum command from thecontroller, the valve to the reservoir is always open. The number ofpressure pulses in the initial period is increased from one to ten asthe pumping command increase from zero to 100%.

After the initial pumping period, there is a transition to theend-of-stroke pumping period. In this respect, software filters arepreferably used to determine when a stroke ends, with at least fivepressure pulses used in the end-of-stroke period for the end-of-strokefilters to initialize. The end-of-stroke period ends when the end ofstroke is detected. During the end-of-stroke period, the valve open timeof the pressure pulse is preferably 83.3 ms (50% duty cycle at 16 Hz).FIGS. 7 and 8 show the pressure pulses during the initial andend-of-stroke periods. FIG. 7 shows pressure pulses for a low-flowcommand by the controller, and FIG. 8 shows a pressure pulse for alarge-flow command by the controller. Note that the on time for a pulseis much longer for higher commands.

The pressure pulses generate a ripple in the measured pressure in theactuation chamber while the membrane is moving. By filtering andisolating this pressure ripple, the end-of-stroke algorithm can detectwhen the diaphragm has reached the chamber wall and stopped moving. Thisend-of-stroke information may be used for flow calculations and forsequencing the pump pods for fill and expel strokes.

In the first stage of filtering, the pressure signal for each pump podis passed through a band-pass filter. This filter is used to isolate thepulse-pumping frequency. As discussed above, the pulse-pumping frequencypreferably increases from 2 Hz to 16 Hz as the pumping command increasesfrom 0% to 100%. FIG. 9 shows the output of the band-pass filter.

The absolute value of this filtered signal is then passed through asecond-order low-pass filter with a damping ratio of one. The cornerfrequency of this filter is varied based on the pulse pumping frequency.FIG. 10 shows the output of this low-pass filter. The output from thelow-pass filter is divided by the absolute value of the supply pressureto normalize the ripple value. This final value of the pressure rippleis then used to detect the end of stroke. Once in the end-of-strokeperiod, this ripple characteristically drops down to zero when thediaphragm is stopped by the chamber wall.

FIG. 11 is a graph showing pressure measurements in the actuationchambers of each of the pump pods in the disposable unit, and alsoshowing the results of the filtering described above. It should be notedthat the unfiltered pressure readings show that the two pump pods areout of phase, with one pump pod expelling liquid while the other isfilling with liquid. As can be seen in the plots of filtered readings,these filtered readings drop to zero at the end of each stroke.

At the end of the stroke, the flow rate is calculated for a given pumppod and flow direction by dividing the chamber volume by the time forthe stroke to complete. Once the expel stroke has ended, the variablesfor the stroke are reset, and this process repeats for the fill stroke.

The pressure ripple causes pressure readings to vary significantly forthe duration of the stroke. Thus, an average pressure is calculated andlogged. As shown in FIG. 12, the average pressure is preferably computedby integrating pressure between the fifth and tenth pulse. In thisembodiment, the fifth and tenth pulses are chosen as the start and endof the average to ignore effects of the pressure when initiating thestroke and when the diaphragm hits the chamber wall.

To check whether any of the pressure transducers (theactuation-chamber-pressure transducer 44, thepositive-reservoir-pressure transducer 45 or thenegative-reservoir-pressure transducer 46) may be malfunctioning, thecontroller preferably compares pressure readings at the end of a stroke.Referring to FIG. 4, at the end of an expel stroke, while thepositive-supply valve 47 is open, the pressure reading of theactuation-chamber-pressure transducer 44 is compared to the reading ofthe positive-reservoir-pressure transducer 45. Since at the end of theexpel stroke the pressure readings from these two transducers should bethe same, any difference in pressure readings from these two transducersindicates a malfunction in one of the two transducers. Similarly, at theend of a fill stroke, while the negative-supply valve 48 is open, thecontroller 49 preferably compares the pressure reading of theactuation-chamber-pressure transducer 44 to the reading of thenegative-reservoir-pressure transducer 46. If the controller detects asignificant change in these pressure readings, the controller generatesan alarm signal indicating a malfunction in one of the transducers.

The controller can also detect aberrant flow conditions by integratingthe pressure readings over time to obtain a measure of the work done inmoving the liquid. If the amount of work done goes up or down, thecontroller preferably generates an alarm signal indicating thatsomething has gone wrong in the line, such as an occlusion, a leak, or adisconnect. The ability to detect a disconnect or a leak may beimportant, particularly when pumping blood or other life-criticalfluids, because of the relatively large flow rates of fluids beingpumped. In one embodiment, by integrating the pressure readings anddetermining the work function, the controller can detect a linedisconnect within approximately three seconds.

This calculation can also take into account the head height between thepod pumps and the patient, although this height may be assumed to beconstant during a thermal-therapy procedure. This calculation can berepresented asK _(fluidpath) ×m _(pod)=∫_(stroke)(P _(pod) −P _(height) _(—)_(diff))dtwhere

-   -   K_(fluidpath) is the resistance in the fluid path,    -   m_(pod) is the mass of fluid contained in the pod,    -   P_(pod) is the pressure in the pump pod, and    -   P_(height) _(—) _(diff) is the pressure due to head height        between the pod and the patient.        Since both K_(fluidpath) and m_(pod) should be constant during a        thermal therapy procedure, any variation in the integrated        pressure should indicate a change in resistance in the fluid        and/or a change in the amount of mass displaced during a stroke,        and thus indicate an aberrant flow condition, such as an        occlusion or a disconnect.

In one embodiment, the head height is not monitored during theprocedure. The head height is calculated based on the first few pumps ofthe pod. Those first few pumps set the standard for the head heightcalculation, based on the following calculationP _(pod) =K _(fluidpath) m′+P _(height) _(—) _(diff)where m′ is the mass flow rate.

In particular, since normally the flow rate is low in the first fewstrokes of the pod, m′ may be assumed to be zero and the pressure in thepod equal to the head pressure; P_(pod)=P_(height) _(—) _(diff). Basedon this calculation, the head height is presumed to be constant.

In one embodiment, the controller looks for a change in the integratedpressure between consecutive strokes or a change (with a smallertolerance) over three strokes of the low-pass filtered value of theintegrated pressure. If either of these changes is excessive, an erroris declared and pumping is stopped until a medical technicianintervenes. This detection algorithm is not run during priming due tothe large variations in the integrated pressure signal that occur whenthere is a mixture of air and liquid in the pods.

Another method of detecting occlusions at low flow rates may be run intandem with the pod-pressure-integration method. In this method, thecontroller looks for multiple consecutive short strokes of the exactsame length. If such strokes are detected, the pod pump is probably notcompleting strokes due to an occlusion or a pneumatic problem. In oneembodiment, if more than six short strokes occur on a given pod pump, anerror signal is generated. During priming, this detection method is notused because fast, short strokes are common when the chambers are filledwith air.

If the end of a stroke does not occur within a predetermined number ofpressure pulses (e.g., 100 pressure pulses as discussed above inconnection with FIGS. 7-12), the controller preferably generates anerror signal. Excessive time to complete a stroke may indicate apneumatic leak. Such a check can be run during priming as well as duringthe procedure.

2.4. Fluid Flow Management

Generally speaking, a single pump pod operates in a pulsatile fashion,first drawing in fluid and then pumping out fluid. Pulsatile operationmay be necessary, desirable, or inherent in certain applications (e.g.,extracorporeal blood treatment in which blood is drawn from a patientand returned to the patient through a single needle is inherentlypulsatile, since blood generally cannot be drawn from the patient andpumped back into the patient at the same time through the singleneedle).

In a dual pump configuration, the two pump pods may be operated from azero degree phase relationship (i.e., both pumping chambers act in thesame direction) to a 180 degree phase relationship (i.e., the pumpingchambers act in opposite directions). A zero degree phase relationshipcan be used to produce a substantially pulsatile fluid flow, similar toa single pump pod. A 180 degree phase relationship can be used toproduce a substantially continuous fluid flow both toward the pumps andfrom the pumps. A 90 degree phase relationship can be used to produce asubstantially sinusoidal fluid flow. FIGS. 74A-74C show plots for volumeflow, pod volumes, and total hold up flow for a zero degree phaserelationship, a 180 degree phase relationship, and a 90 degree phaserelationship, respectively.

In some applications, it may be necessary or desirable to providesubstantially continuous fluid flow to the pump pod(s) and/or from thepump pod(s). As discussed above, substantially continuous fluid flow maybe provided using two pump pods operating with a 180 degree phaserelationship. For one or more pump pods operating in a pulsatile mode(e.g., a single pump pod or two pump pods operating in a zero degreephase relationship), one way to produce a more continuous fluid flowoutput is to fill the pump pod(s) as quickly as possible and then pumpout the fluid over an extended period of time (e.g., the desired delivertime could be set to be a total desired stroke time minus the time thatthe fill stroke took).

Even when operating two pump pods in a 180 degree phase relationship, itis possible for there to be discontinuous fluid flow under someconditions, particularly when the input impedance is significantlydifferent than the output impedance. For example, in extracorporealblood treatment applications, input impedance may be higher than outputimpedance due to such things as needle size (e.g., the needle used todraw blood from the patient may be smaller than the needle used toreturn blood to the patient), blood viscosity (e.g., the patient mayhave very viscous blood that is thinned as part of the treatment), orpoor patient access (e.g., poor patient circulation may limit the rateat which blood can be drawn). Such impedance differences can result indifferent pump pod fill and delivery times, particularly if the systemcannot be balanced by applying more pressure to one pump pod than theother pump pod (in theory, it should be possible to ensure a precise 180degree phase relationship if there were no limit on the amount ofpneumatic pressure that could be applied to the pump pods, but there aretypically both physical limits—the maximum pressures in the tworeservoirs—and practical limits to the amount of pressure that can beapplied). Therefore, in some situations, the stroke of one pump podmight finish before the corresponding stroke of the other pump pod, inwhich case it may be necessary to delay the former pump pod while thelatter pump pod completes its stroke, resulting in a pause in the fluidflow produced by the former pump pod. One possible solution is to limitthe flow rate to the slowest of the fill and deliver strokes. Althoughthis would result in slower blood delivery flow rates, the flow ratewould still be known and would be continuous.

2.5. Alternative Embodiment Using Variable-Restriction Pneumatic Valves

As noted above, the positive-supply valve 47 and the negative-supplyvalve 48 in the pneumatic actuation system 40 of FIG. 4 may bevariable-restriction valves, as opposed to binary on-off valves. Byusing variable valves, the pressure applied to the actuation chamber 42and the membrane 33 can be more easily controlled to be just a fractionof the pressure in reservoirs 51, 52, instead of applying the fullreservoir pressure to the membrane. This facilitates use of the samereservoir or set of reservoirs for pump pods having different operatingparameters, such as pump volume, pump stroke size, or pump actuationpressure. Of course, the reservoir pressure generally needs to begreater than the desired pressures to be applied to various pump pod'smembranes, but one pump pod may be operated at, say, half of thereservoir pressure, and another pump pod may be actuated with the samereservoir but at, say, a quarter of the reservoir pressure. Thus, eventhough different pump pods may be designed to operate at differentpressures, these pump pods may all share the same reservoir or set ofreservoirs but still be actuated at different pressures, through the useof variable valves. The pressures used in a pump pod may be changed toaddress conditions that may arise or change during pumping. For example,if flow through the system's tubing becomes constricted because thetubes get twisted, one or both of the positive or negative pressuresused in the pump pod may be increased in order to compensate for theincreased restriction.

FIG. 28 is a graph showing how pressures applied to a pod pump may becontrolled using variable valves. The vertical axis represents pressurewith P_(R+) and P_(R−) representing respectively the pressures in thepositive and negative reservoirs (items 51 and 52 in FIG. 4), and P_(C+)and P_(C−) representing respectively the positive and negative controlpressures acting on the pump pod's membrane. As can be seen in FIG. 28,from time T₀ to about time T₁, a positive pressure is applied to theactuation chamber (so as to force fluid out of the pumping chamber). Byrepeatedly reducing and increasing the flow restriction caused by thepositive variable valve (item 47 in FIG. 4), the pressure being appliedto the actuation chamber can be held at about the desired positivecontrol pressure, P_(C+). The pressure varies, in a sinusoidal manner,around the desired control pressure. An actuation-chamber pressuretransducer (item 44 in FIG. 4) in communication with the actuationchamber measures the pressure in the actuation chamber and passes thepressure-measurement information to the controller (item 49 in FIG. 4),which in turn controls the variable valve so as to cause the actuationchamber's pressure to vary around the desired control pressure, P_(C+).If there are no fault conditions, the membrane is pushed against a rigidwall of the pumping chamber, thereby ending the stroke. The controllerdetermines that the end of stroke has been reached when the pressuremeasured in the actuation chamber no longer drops off even though therestriction created by the variable valve is reduced. In FIG. 28, theend of the expelling stroke occurs around time T₁. When the end ofstroke is sensed, the controller causes the variable valve to closecompletely so that the actuation chamber's pressure does not increasemuch beyond the desired control pressure, P_(C+).

After the positive variable valve is closed, the negative variable valve(item 48 in FIG. 4) is partially opened to allow the negative pressurereservoir to draw gas from the actuation chamber, and thus draw fluidinto the pumping chamber. As can be seen in FIG. 28, from a time shortlyafter T₁ to about time T₂, a negative pressure is applied to theactuation chamber). As with the expelling (positive pressure), strokedescribed above, repeatedly reducing and increasing the flow restrictioncaused by the negative variable valve can cause the pressure beingapplied to the actuation chamber can be held at about the desirednegative control pressure, P_(C−) (which is weaker than the pressure inthe negative pressure reservoir). The pressure varies, in a sinusoidalmanner, around the desired control pressure. The actuation-chamberpressure transducer passes pressure-measurement information to thecontroller, which in turn controls the variable valve so as to cause theactuation chamber's pressure to vary around the desired controlpressure, P_(C−). If there are no fault conditions, the membrane ispulled against a rigid wall of the actuation chamber, thereby ending thedraw (negative pressure) stroke. As described above, the controllerdetermines that the end of stroke has been reached when the partialvacuum measured in the actuation chamber no longer drops off even thoughthe restriction created by the variable valve is reduced. In FIG. 28,the end of the draw stroke occurs around time T₂. When the end of strokeis sensed, the controller causes the variable valve to close completelyso that the actuation chamber's vacuum does not increase much beyond thedesired negative control pressure, P_(C−). Once the draw stroke hasended, the positive variable valve can be partially opened to begin anew expelling stroke with positive pressure.

Thus, two variable-orifice valves may be used to throttle the flow fromthe positive-pressure source and into the negative-pressure. Thepressure in the actuation chamber is monitored and a controller usesthis pressure measurement to determine the appropriate commands to bothvalves to achieve the desired pressure in the actuation chamber. Twoadvantages of this arrangement are that the filling and deliveringpressure may be precisely controlled to achieve a desired flow ratewhile respecting pressure limits, and that the pressure may be variedwith a small sinusoidal signature command. This signature may bemonitored to determine when the pump reaches the end of a stroke.

Another advantage of using variable valves in this way, instead ofbinary valves, is that by only partially opening and closing thevariable valves the valves are subject to less wear and tear. Therepeated “banging” of binary valves all the way opened and all the wayclosed can reduce the life of the valve.

If the end of stroke is detected and the integrated value of thecorrelation function is very small, this may be an indication that thestroke occluded and did not complete properly. It may be possible todistinguish upstream occlusions from downstream occlusions by looking atwhether the occlusion occurred on a fill or a delivery stroke (this maybe difficult for occlusions that occur close to the end of a stroke whenthe diaphragm is near the chamber wall). FIGS. 73A-73B depict occlusiondetection (lines 2703 and 2704 represent when occlusion is detected) inaccordance with an exemplary embodiment of the present invention.

Under normal operation, the integrated value of the correlation functionincreases as the stroke progresses. If this value remains small or doesnot increase, then the stroke is either very short (as in the case of avery low impedance flow or an occlusion) or the actual pressure may notbe tracking the desired sinusoidal pressure, e.g., due to a bad valve orpressure signals. Lack of correlation can be detected and used for errorhandling in these cases.

Under normal circumstances when the flow controller is running, thecontrol loop preferably adjusts the pressure for any changes in flowrate. If the impedance in the circuit increases dramatically and thepressure limits are saturated before the flow has a chance to reach thetarget rate, the flow controller generally will not be capable ofadjusting the pressures higher to reach the desired flow rate. Thesesituations may arise if a line is partially occluded (e.g., a blockage,such as a blood clot in a blood pumping embodiment) has formed in thecircuit. Pressure saturation when the flow has not reached the targetflow rate can be detected and used in error handling.

If there are problems with the valves or the pneumatics, such as aleaking fluid valve or a noisy pressure signal, ripple may continue onthe stroke indefinitely and the end of stroke algorithm may not seeenough of a change in the pressure ripple to detect end of stroke. Forthis reason a safety check is preferably added to detect if the time tocomplete a stroke is excessive. This information can be used for errorhandling.

2.6. Exemplary Applications for Pump Pods

Reciprocating positive-displacement pumps and related control systems ofthe types described above may be used in a wide variety of fluid pumpingapplications, and are particularly well-suited for (although not limitedto) use in applications that involve artificial or extracorporeal bloodpumping such as, for example, hyperthermic or hypothermic bloodtreatments, hemodialysis and other blood processing and filteringtreatments (e.g., plasmapheresis and apheresis), cardiac bypass andother assisted blood circulation treatments (e.g., ventricular assist),cardioplegia (as part of cardiac bypass or otherwise), lung bypass orartificial lung and other applications involving extracorporeal bloodoxygenation, and chemotherapy and other drug treatments (e.g., regionalhyperthermic chemotherapy), to name but a few. For example, in certainembodiments, reciprocating positive-displacement pumps and relatedcontrol systems of the types described above may be used in aheat-exchanger system that can be used to heat or cool a fluid such asblood. Exemplary heat-exchanger systems are described below.

3. Exemplary Heat-Exchanger Systems

Embodiments of the present invention relate generally to heat-exchangersystems that can be used to heat or cool a fluid such as blood. A bloodheating system may be particularly useful for whole-body hyperthermictreatments (e.g., to raise the body temperature to combat hypothermia orto combat certain diseases, such as Hepatitis C and possibly some typesof cancer, HIV/AIDS, rheumatoid arthritis and psoriasis) or for regionalhyperthermic chemotherapy treatments. Exemplary heat-exchanger systemsare described below, one in the context of the pumping and heating ofblood as part of whole-body hyperthermic treatment, and the other in thecontext of regional hyperthermic chemotherapy treatment. Of course, itshould be noted that such a heat-exchanger systems may be used in otherapplications for heating and/or cooling fluid. Furthermore, while theexemplary heat-exchanger systems described below incorporate pump podsof the types described above, it should be noted that embodiments arenot limited to the use of pump pods. Other types of pumps may be usablein various alternative embodiments.

3.1. Whole-Body Hyperthermic Treatment

As discussed above, a blood heating system may be used for whole-bodyhyperthermic treatments (e.g., to raise the body temperature to combathypothermia or to combat Hepatitis C by raising the core bodytemperature to a sufficient level so as to purge the virus from infectedliver cells). Generally speaking, whole-body hyperthermic treatment forHepatitis C involves raising the core body temperature to approximately41.6 degrees Celsius (107 degrees Farenheit) for an extended period oftime. A typical treatment might last three to four hours, including a30-60 minute warm-up period, 80-120 minute plateau period, and 30-45minute cool-down period. Core body temperature, and therefore fluidtemperature generated by the heat-exchanger system, must be controlledcarefully to maintain the patient at the target core temperature withlittle variation—if the core temperature is too low, then the treatmentmay not be effective; if the core temperature gets too high, then thepatient can be harmed.

FIG. 24 is a schematic view of a whole-body hyperthermic treatmentsystem in accordance with an exemplary embodiment of the presentinvention. Blood leaves the patient via the 14F left femoral venouscannulae. Within the heat-exchanger system 10, the blood is pumped bytwo pump pods through a heat exchanger for heat exchange. A controlsystem monitors various parameters (e.g., blood temperature entering andexiting the heater/cooler as well as patient core temperature) andadjusts operation of the pump pods and the heater/cooler accordingly.following the heat exchanger, the blood passes through a particulate andair filter and returns to the patient via the 12F right femoral venouscannulae. During this procedure, the patient is typically supine,intubated, anesthetized, and monitored by a doctor or otherprofessional.

3.1.1. Exemplary Heat Exchanger Systems

FIG. 1 shows a heat-exchanger system 10 in accordance with an exemplaryembodiment of the present invention. The heat-exchanger system 10includes a base unit 11 and a disposable unit 16. As described furtherbelow, the disposable unit 16 is installed into the base unit 11 suchthat a heat-exchanger bag (e.g., a heat-exchanger bag 21 as shown inFIGS. 2 and 48) of the disposable unit 16 rests within a heat exchangerportion of the base unit 11. As blood from a patient circulates throughthe disposable unit 16, and specifically through the heat-exchanger bag21, the blood is heated by the heat exchanger and is returned to thepatient. During such circulation, the blood remains within thedisposable unit 16 and generally does not come into contact withcomponents of the base unit 11. The disposable unit 16 is considered tobe “disposable” in that it is generally discarded after a patienttreatment, whereas the base unit 11 can be re-used repeatedly by simplyinstalling a new disposable unit 16. In fact, the base unit 11 mayinclude mechanisms to prevent re-use of a disposable unit (e.g., using abar code, RFID tag, or other identifier associated with the disposableunit).

3.1.2. Exemplary Base Unit

FIG. 25 shows the base unit 11 in accordance with an exemplaryembodiment of the present invention. FIG. 47A shows some of the interiorcomponents of the base unit 11 in accordance with an exemplaryembodiment of the present invention, while FIG. 47B shows a rearperspective view of the base unit 11. The base unit 11 includes, amongother things, a heat exchanger 2541, a pneumatic actuation system 40, adisposables interface 2500 (also referred to as a manifold interface), apatient interface, a controller, a user interface console 13, and aventilation system 2701. The pneumatic actuation system 40 may begenerally of the type shown in FIG. 4, but with separate pneumaticinterfaces, valves, and sensors for each of two pump pods. Thedisposables interface may include two sensors that provide both thermaland electrical connectivity to a disposable unit to allow for monitoringblood temperature both upstream and downstream of the heat exchanger andalso to allow for monitoring other parameters, as discussed below. Thepatient interface may include one or more temperature inputs 2702 forreceiving temperature information (specifically patient temperatureinformation) from one or more temperature probes. The user interfaceconsole allows the user to control and monitor operation of the system.In an exemplary embodiment, the controller controls operation of theheat exchanger and the pump pods based on, among other things, bloodtemperature information received from the disposables interface,pressure information received from the pneumatic actuation system,patient temperature information received from the patient interface, anduser inputs received from the user interface console.

3.1.3. Exemplary Disposable Unit Configurations

As mentioned above, a disposable unit for a heat-exchanger systemtypically includes a heat-exchanger bag through which blood flows whilepassing through the heat exchanger. The heat-exchanger bag may includeone or more fluid paths. In one exemplary embodiment described below, aheat-exchanger bag includes a single fluid path connecting two fluidinlets to a common fluid outlet. In another exemplary embodimentdescribed below, a heat-exchanger bag includes a single fluid pathhaving a single inlet and a single outlet. Heat-exchanger bags aretypically made of a flexible plastic material, although theheat-exchanger bag may be made from other materials and may include ametallic material or other material to improve thermal conductivity.

FIG. 2 shows relevant components of a disposable unit 16, in accordancewith an exemplary embodiment of the present invention. The disposableunit 16 includes, among other things, a heat-exchanger bag 21 (alsoreferred to as a “flow-path bag”) with a manifold 130 and a panel 2017holding (or configured to hold) two pump pods 25 a and 25 b and afilter/air trap 29. The disposable unit 16 preferably also includes ahandle (not shown here, but shown in FIG. 48) that is used tomechanically interconnect the above-referenced components into acohesive unit that can be readily installed into the base unit 11, whichpreferably includes a manifold interface (described below) for receivingthe manifold 130 and providing pneumatic connections for operating thepumps 25 a, 25 b. The bag 21 includes a fluid path 150 through whichfluid can be pumped. In this embodiment, the manifold 130 is integratedwith the heat-exchanger bag 21 and is configured with appropriate tubingconnections and supports that are used to interconnect theheat-exchanger bag 21 with the two pump pods 25 a and 25 b.

In the embodiment shown in FIG. 2, the manifold 130 includes twoflow-path inlets 23 a and 23 b (also referred to as “heat-exchanger baginlets”) in fluid communication with one end of the fluid path 150 and aflow-path outlet 27 (also referred to as a “heat-exchanger bag outlet”)in fluid communication with the other end of the fluid path 150. Theblood is preferably pumped from the patient and through theheat-exchanger bag 21, in this embodiment by a pair of self-containedpump pods 25 a, 25 b (referred to individually as a pump pod 25), whichare preferably reciprocating positive-displacement pumps of the typesdescribed herein. In this embodiment, the manifold 130 includespneumatic passageways 138 a, 138 b to facilitate establishment ofpneumatic connections respectively to the pump pods 25 a, 25 b(typically using tubing). It should be noted that embodiments are notlimited to the use of two pump pods or, for that matter, to the use ofpump pods. The manifold 130 is described more fully below.

In this embodiment, each pump pod 25 includes an inlet 34 and an outlet37 (i.e., pump pod 25 a has an inlet 34 a and an outlet 37 a, while pumppod 25 b has an inlet 34 b and an outlet 37 b). The various componentsmay be interconnected in at least two configurations. In a firstconfiguration shown in FIGS. 48 and 72, the pump pods 25 a, 25 b may becoupled upstream of the heat-exchanger bag 21 such that the pump inlets34 a, 34 b are coupled to receive blood directly from the patient (e.g.,through a “Y” connector 2024), the pump outlets 37 a, 37 b are connectedrespectively to the heat-exchanger-bag inlets 23 a, 23 b by tubes 2026a, 2026 b, and the filter/air trap 29 is connected to theheat-exchanger-bag outlet 27 by tube 2027. In this way, the pump pods 25a, 25 b are operable to urge blood through the heat-exchanger bag 21,from which the blood exits through the flow-path outlet 27 and thenpasses through the filter/air trap 29 before returning to the patient.In a second configuration (not shown), the pump pods 25 a, 25 b may becoupled downstream of the heat-exchanger bag 21 such that blood from thepatient enters the heat-exchanger-bag inlets 23 a, 23 b (e.g., through a“Y” connector, not shown), the pump inlets 34 a, 34 b are coupled to theflow-path outlet 27 (e.g., through a “Y” connector, not shown), and thepump outlets 37 a, 37 b are coupled (e.g., through a “Y” connector, notshown) to return blood to the patient via the filter/air trap 29. Inthis way, the pump pods 25 a, 25 b draw blood through the heat-exchangerbag 21 and pump the blood through the filter/air trap 29 to the patient.It should be noted, in an alternate embodiment, the heat-exchanger bag21 could include separate outlets, which could facilitate its couplingwith the pump pods in some situations. In the embodiments shown in FIGS.2 and 48, the filter/air trap 29 is preferably provided with a purgeport to allow air to escape from the filter. FIG. 48 shows a data keyslot 2542 in which a data key can be placed, for example, duringmanufacturing.

FIG. 81 shows a variation of the disposable unit 16 of FIG. 48 includinga patient connection circuit 2060 having a sterile protective covering2062, in accordance with an exemplary embodiment of the presentinvention. Specifically, a configuration of tubing 2061 is connectedbetween the pump pod inlets and the filter outlet to form a completecircuit. In this embodiment, the tubing 2061 includes an airpurge/sample port 2019 and a blood monitoring interface optionallyincluding shunt sensor connections 2020 and/or disposable H/S cuvette2022. In order to effectuate connections to the patient, the surgeon orother technician typically cuts through the tubing 2061 at or about thedistal portion of the tubing (in this embodiment, the U-shaped portiontoward which the arrow for reference numeral 2060 points, which may bereferred to as the “circus maximus”) in order to create two tube ends.The surgeon or technician can then connect appropriate needles to thetwo tube end for insertion into the patient.

In this embodiment, the distal portion is sterilized and covered with athin plastic protective material 2062 in order to maintain sterility.Prior to cutting through the tubing 2061, a portion of the tubing 2061in the sterile field is exposed, for example, by pulling on theprotective material 2062 in opposite directions until it separates. FIG.82 shows a representation of the patient connection circuit from FIG. 81with a portion of tubing 2061 exposed through the sterile protectivecovering 2062, in accordance with an exemplary embodiment of the presentinvention. Once the section of tubing 2061 has been exposed, a cut canbe made at location 2063.

FIG. 83 shows a variation of the disposable unit of FIG. 81 including anadditional fluid delivery line 2065, in accordance with an exemplaryembodiment of the present invention. The fluid delivery line 2065 is influid communication with the pump pod inlets to that fluid from thefluid delivery line 2065 (e.g., IV fluids) can be incorporated into thepatient blood and circulated through the heat exchanger and into thepatient. In this embodiment, the fluid delivery line 2065 is configuredwith a connector 2064 (e.g., a needle for introduction into an IV bag)in order to facilitate connection with a fluid source.

FIGS. 15, 16 and 17 show respectively top perspective, end perspective,and top plan views of an alternative heat-exchanger bag 121 inaccordance with another embodiment of the present invention. In thisembodiment, the bag 121 has a single inlet 123, a single outlet 127, anda flow path 150 extending between the inlet 121 and the outlet 123. Theinlet 123 and the outlet 127 of this bag 121 are spaced away from eachother, whereas in the bag 21 of FIGS. 2 and 48, the inlet 23 a, 23 b andoutlet 27 are adjacent each other. Having the inlet and outlet adjacenteach other (like the bags shown in FIGS. 2 and 48) generally makes thedisposable unit less bulky to handle. The bag 121 may be formed from twosheets of plastic or other appropriate material that are welded at theseams to produce the flow path 150.

It should be noted that alternative embodiments may employ other pumppod configurations as part of the disposable unit 16. For example,various alternative embodiments could employ the pump pod assembly 2004shown in FIGS. 5A and 5B, the pump cassette 2015 shown in FIGS. 22A and22B, or the dual-housing arrangement 2016 shown in FIG. 23. With regardto pump pod assembly 2004, the common inlet 54 may be coupled to receiveblood from the patient and the common outlet 57 may be coupled toprovide blood to the heat-exchanger bag 21, or the common inlet 54 maybe coupled to receive heated blood from the heat-exchanger bag 21 andthe common outlet 57 may be coupled to provide blood to the filter/airtrap 29. Similarly, with regard to pump cassette 2015, the common inlet2005 may be coupled to receive blood from the patient and the commonoutlet 2006 may be coupled to provide blood to the heat-exchanger bag21, or the common inlet 2005 may be coupled to receive heated blood fromthe heat-exchanger bag 21 and the common outlet 2006 may be coupled toprovide blood to the filter/air trap 29.

It should be noted that various components of the disposable unit 16 maybe provided separately and/or in various assemblies and sub-assemblies,and therefore the word “unit” is not intended to require that thedisposables be provided as a complete system or kit. Thus, for example,the pump pods (or pump pod assemblies/cassettes) could be providedseparately from the rest of the disposable unit 16. Among other things,providing the pump pods separately could allow pump pods of differentvolumes to be easily integrated, without requiring separate versions ofthe main disposable unit for different pump volumes. Furthermore, thedisposable unit 16 could be provided with some tubing connectionsalready in place, e.g., with the pump outlets 37 a, 37 b already coupledto the heat-exchanger-bag inlets 23 a, 23 b and/or with the pump inlets34 a, 34 b already coupled to a “Y” connector and/or with the flow-pathoutlet 27 already coupled to the filter/air trap 29.

In typical embodiments, the same controller 49 preferably controls bothpump pods (items 25 a and 25 b of FIGS. 2 and 48) of the disposable unit16, and preferably (although not necessarily) causes the two pump podsto pump out of phase (i.e., one pumping chamber is emptying while theother is filling) during normal blood-pumping operation in order toprovide for more continuous flow to/from the patient and through theheater. Some ways in which the controller 49 may monitor and control thepumps, heaters, and other components are discussed above as well asfurther below.

3.1.4. Exemplary Heat Exchanger Components

FIG. 13A shows greater detail of the heat exchanger 2541 shown in FIG.25. In this embodiment, an upper heating plate 12 is mounted in a door18 located at the top of the base unit. A lower heating plate 14 islocated in the base unit 11 under the door 18. The heat-exchanger bag21, which is part of the disposable unit 16, is placed on top of thelower heating plate 14, such that when the door 18 is closed, the bag 21rests between the two heating plates 12, 14. This arrangement generallypermits more heat to be transferred to the blood more quickly than asingle-plate arrangement would, although alternative embodiments may usea single plate either above or below the heat-exchanger bag 21 and/ormay use other types of heating elements. The door 18 and/or the upperplate 12 may include pneumatic sealing tracks to evacuate air from theheat exchanger or produce a better coupling between the upper plate 12and the bag 21 (e.g., by producing a vacuum that pulls the upper surfaceof the bag 21 into contact with the upper plate 12.

Each of the heating plates 12, 14 may include a single heating elementor multiple heating elements. The heating elements are typically(although not necessarily) electric heating elements. FIG. 14 shows anexploded view of one exemplary heating element configuration in whichthe upper heating plate 12 includes a single heater element 141 and aplaten 142 and the lower heating plate 14 includes a single heaterelement 143 and a platen 144. FIG. 18 shows an alternative heatingelement configuration in each of the heating plates 12, 14 includesseven heating elements 182, 183, 184, 185. In practice, electricitypassing through the heating elements heats the heating elements, whichin turn heat the platens, which in turn conduct heat to the bloodpassing through the heat-exchanger bag. It should be noted that heatingelements can be used without platens, although the platens tend toprovide a more even distribution of heat. In the embodiment shown inFIG. 18, if one or even several of the heating elements fails, the heatexchanger should still be able to perform at least some blood heating,since the platens generally can still be heated with fewer than all theheating elements working and still impart heat to the blood passingthrough the heat-exchanger bag.

In order to improve thermal coupling between the heating plates 12, 14and the heat-exchanger bag, the door 18 may produce a substantiallyair-tight seal when closed. Furthermore, air may be evacuated fromaround the heat-exchanger bag to achieve better thermal coupling betweenthe bag and the plates. In this regard, a compressor (not shown) thatmay be used to produce the positive and/or negative pressures for thereservoirs 51, 52 may be used to evacuate air from around theheat-exchanger bag. Cooling fins 131 or other elements may be providedto draw away excess heat.

The temperature inside the heat exchanger may be monitored to ensurethat the blood does not get so heated as to cause damage to the blood.In the embodiment shown in FIG. 18, each heating plate is provided withtwo temperature sensors 180, 181 located near the outlet 27 at pointsnear where the blood should be at its hottest. Since the inlet 23 isnear the outlet 27 (in this figure), the blood flowing through theoutlet may be a little cooler than further upstream, because the coolerblood flowing into the inlet can cool the warmer blood passing throughthe outlet nearby. Three of the heating elements 182, 183, 184 arelocated towards the end of the flow path in the heat-exchanger bag 21.Each temperature sensor 180, 181 may be located between heating elementsand near the outlet 27, and the temperature sensors 180, 181 arepreferably spaced some distance apart with at least one heating elementlocated between them (in this embodiment, heating element 183). Thus, asshown in FIG. 18, one sensor 181 is located between the last two heatingelements 183, 184 that the flow path crosses before the blood exits theoutlet 27. The other sensor 180 is located upstream of both of these twoheating elements 183, 184 and between two heating elements 182, 183. Ifthe two temperature sensors 180, 181 are working properly and if theheat exchanger is working properly, the two temperature sensors shouldhave readings within a certain number of degrees of each other (althoughthey would not typically have the exact same temperature reading). Thecontroller preferably receives temperature information from the twotemperature sensors 180, 181 and may generate an alarm, discontinueoperation, reduce power to the heating elements, and/or take otheraction if either (or both) of the temperature sensors indicates anunsafe temperature or if the difference in temperature readings measuredby the two sensors exceeds a predetermined limit. The maximumtemperature of the plates should not be allowed to exceed the maximumallowable blood temperature, because otherwise, if the flow of bloodwere to stop or slow, the blood could be over-heated.

In certain embodiments, one or both of the heating plates 12, 14 may betranslatable in a vertical direction when the door is closed, e.g., tofacilitate evacuation of air from the heat-exchanger bag 21 duringpriming or to squeeze residual blood out of the heat-exchanger bag 21and back into the patient at the end of the blood-heating procedure. Theplates may additionally or alternatively be tiltable so that the bag maybe tilted, e.g., in order to assist in removing air bubbles from the bagduring priming or to assist with returning blood to the patient. Suchvertical translation and/or tilting could be performed manually or couldbe performed automatically, for example, under control of the controller49.

Thus, at the end of the blood-heating procedure, the membranes in thepump pods 25 a, 25 b may be urged against the pumping-chamber wall so asto minimize the volume of the pumping chambers and expel as much bloodas possible back toward the patient. Furthermore, in embodiments thatinclude vertically translatable and/or tiltable plates, theheat-exchanger bag 21 may be squeezed and/or tilted to direct as muchblood as possible back toward the patient.

3.1.5. Exemplary Manifold and Manifold Interface

FIGS. 49A and 49B respectively show a perspective back-side view and aperspective bottom view of the manifold 130 from FIG. 2, in accordancewith an exemplary embodiment of the present invention. FIG. 49A showsbag inlet and outlet connectors 2053, 2054 for connection at the inletand outlet openings of the fluid channel 150 of the bag 21. The baginlet connector 2053 is in fluid communication with the inlets 23 a, 23b, while the bag outlet connector 2054 is in fluid communication withthe outlet 27. The thermowells 133 a and 133 b are shown in the outletfluid path and the inlet fluid path, respectively. The pneumaticinterfaces 139 a, 139 b that are used to provide pneumatic pressure fromthe base unit 11 to the pneumatic ports 138 a, 138 b are shown.

FIG. 13B shows a perspective back-side cross-sectional view of themanifold 130 of FIGS. 2, 49A, and 49B, in accordance with an exemplaryembodiment of the present invention. In this embodiment, the manifold130 includes an inlet thermowell 133 a located in a bag inlet 23 a andan outlet thermowell 133 b located in a bag outlet 27. The thermowells133 a, 133 b interface with corresponding probes in a manifold interfaceof the base unit 11 (discussed below) when the disposable unit 16 isinstalled in the base unit 11. FIG. 13C shows a close-up view of anexemplary thermowell.

The thermowells 133 a, 133 b provide for both thermal and electricalinterconnections between the base unit 11 and the disposable unit 16.Among other things, such thermal and electrical interconnections allowthe controller 49 to monitor blood temperature as the blood enters andexits the heat-exchanger bag 21 and also allow the controller 49 to takeother measurements (e.g., to detect the presence of blood or air in theheat-exchanger bag 21 and to perform leak detection) as discussed below.In this embodiment, each of the thermowells 133 a, 133 b is coupled soas to have a portion residing directly in the fluid path (i.e., incontact with the blood) so as to permit better transmission of bloodtemperature from the disposable unit 16 to the base unit 11. In lieu of,or in addition to, the thermowells, the disposable unit 16 may includeother temperature probes/sensors and interfaces by which the controller49 can monitor blood temperature as the blood enters and exits theheat-exchanger bag 21.

While the exemplary embodiment shown in FIGS. 13B, 49A, and 49B includethermal wells for transmitting thermal information to the base unit 11and optionally for use in conductivity sensing, it should be noted thatother types of sensor components may be additionally or alternativelyused. For example, rather than using a thermal well, a sensor componentthat sends temperature measurements or signals to the base unit 11 maybe used. Various types and configurations of sensors are describedbelow.

Additionally, the manifold 130 includes various tube supports to holdstubes extending from the pumps (items 25 a, 25 b in FIG. 2) and theheat-exchanger bag (item 21 in FIG. 13A). These tubes include the tubesleading from the outlets (items 37 a, 37 b in FIG. 2) of the pumps intothe inlets 23 a, 23 b of the heat-exchanger bag. The outlet 27 of theheat-exchanger bag is also held by the tube support. In a preferredembodiment, the tube support 130 also holds tubes leading to thepneumatic ports (item 38 of FIG. 3) of the pumps and provides theinterface between pumps' pneumatic ports and base unit's pneumaticactuation system (item 40 of FIG. 4). The tubes from the pneumatic portspass into the pneumatic passageways 138 a, 138 b in the tube support130; the pneumatic passageways 138 a, 138 b are respectively in fluidcommunication with the pneumatic interfaces 139 a, 139 b. The pneumaticinterfaces 139 a, 139 b connect to receptacles in the base unit, and thereceptacles in turn provide fluid communication with pneumatic actuationsystems for each of the pumps. This arrangement allows the disposableunit's interface to the base unit to be manufactured more easily andeases the installation of the disposable unit in the base unit. Insteadof manufacturing the pumps so that the pneumatic ports are properlypositioned with respect to each other for installation into the baseunit, the more compact tube support 130 holds the pneumatic interfaces139 a, 139 b in the proper position; the smaller size and simplerstructure of the tube support 130 makes it easier to manufacture thepneumatic interfaces 139 a, 139 b with the desired tolerances forinstallation into the base unit 11. The disposable unit 16 may alsoinclude a data key or other feature for interfacing with the base unit11 in order to provide relevant information to the base unit 11 (e.g.,disposable unit serial number and prior usage information) and/or storeinformation provided by the base unit 11 (e.g., usage information).

A similar arrangement may be used with disposable cassettes that includepneumatically actuated pumps and/or valves. As discussed above, if thenumber of pneumatically actuated pumps and/or valves in a cassette islarge enough, the cassette containing these pumps and valves can becomeso large—and the pressures involved can become so great—that it maybecome difficult to properly seal and position all of the pumps andvalves. This difficulty may be alleviated by placing the valves andpumps in a main cassette, from which connecting tubes lead frompneumatic ports, so that pneumatic communication is provided betweenvalves and pumps in the main cassette and a smaller, secondarytube-support cassette, which is provided with a pneumatic interface foreach of the tubes, as shown in FIG. 23. In this way, the properpositioning and sealing of all the pneumatic interfaces can beaccomplished more easily with the smaller tube-support cassette than itwould be if the pneumatic actuation needed to be applied to the largermain cassette directly. Additionally, or alternatively, valves in themain cassette may be ganged to together in some embodiments, so thatseveral valves may be actuated simultaneously through a single pneumaticinterface on the tube-support cassette and through a single connectingtube between the pneumatic interface and the valves.

FIG. 26 shows a close-up view of the manifold interface 2500 shown inFIG. 25. The manifold interface 2500 includes, among other things,probes 61, 62 and pneumatic ports 2539 a, 2539 b. With reference againto FIG. 13B, it can be seen that the manifold 130 can be installed inthe manifold interface 2500 such that the probes 61, 62 interfacerespectively with the thermowells 133 a, 133 b and the pneumatic ports2539 a, 2539 b interface respectively with the pneumatic interfaces 139a, 139 b. The manifold interface 2500 also includes a data key interface2540 for interfacing with a corresponding data key in the disposableunit. The data key interface 2540 preferably provides a bi-directionalcommunication interface through which the controller 49 can readinformation from the disposable unit (e.g., serial/model number,expiration date, and prior usage information) and write information tothe disposable unit (e.g., usage information). In an exemplaryembodiment, the controller 49 may prevent the start of a treatment ifthe data key is not present or if the disposable unit is unusable, forexample, because it includes an unacceptable serial/model number, ispast a pre-configured expiration date, or has already been used. Thecontroller 49 may terminate a treatment if the data key is removed. Inlieu of a data key interface 2540, the base unit 11 or manifoldinterface 2500 may include other types of interfaces for readinginformation from the disposable unit and/or writing information to thedisposable unit (e.g., RFID, bar code reader, smart key interface).

It should be noted that one or more pumps (e.g., pump pods) may beintegral with a manifold such as the manifold 130 and placed in a baseunit as a single cartridge. The assembly could include pneumaticconnections from the pneumatic ports (which are connected to the baseunit) directly to the pump actuation chambers so that no external tubingwould be needed to make the pneumatic connections to the pump pods. Theassembly could additionally or alternatively include fluidic connections(e.g., from the pump outlets to the interface with the heat-exchangerbag) so that no external tubing would be needed between the pump outletsand the manifold or bag.

3.1.6. Exemplary Blood Heating Schematic

FIG. 6 is a schematic of the disposable unit 16 connections inaccordance with an exemplary embodiment of the present invention. Afterthe disposable unit 16 is primed, an inlet catheter 67 and an outletcatheter 68 are inserted into a vein or veins of a patient. Severalpatient-temperature probes 66 are disposed in or on the patient; theseprobes 66 provide patient-temperature information to the controller inorder to monitor possible overheating of the patient.

The action of the pump pods 25 a, 25 b—which are acted on by the baseunit's pneumatic actuation system (under control of the controller 49)through pneumatic ports 38-raws the blood from the inlet catheter 67into the disposable unit's tubing. The pump pods' inlet and outlet checkvalves 35, 36 ensure that the blood travels in the correct directionthrough the disposable unit's tubing (i.e., in a clockwise direction inthe schematic shown in FIG. 6). After exiting the pump pods 25 a, 25 b,the blood is pumped to the heat-exchanger bag 21, which is preferablyinstalled between two heating plates in the base unit. Before the bloodenters the heating area, the temperature is measured via a bag-inlettemperature sensor 61, which communicates inlet temperature informationto the controller 49. After being heated, the blood's temperature isagain measured via a bag-outlet temperature sensor 62, which alsoprovides temperature information to the controller 49. The heated bloodthen flows through the air trap/filter 29 and then to the patientthrough the return catheter 68.

The controller preferably uses a closed-loop control scheme based on,among other things, patient temperature information (e.g., receivedthrough the patient interface 2704), blood temperature information(e.g., received via the thermal wells in the manifold 130 and thecorresponding sensors in the manifold interface 2500), and pump statusinformation (e.g., reservoir pressure, actuation chamber pressure,end-of-stroke detection, volumetric measurements, air detection,occlusion detection, leak detection) to attain/maintain patient bodytemperature and ensure that blood is not overheated locally (e.g., evenif the patient body temperature is at a safe level, it may be possiblefor the blood to overheat in the heat-exchanger component, for example,if the heat exchanger malfunctions or blood is not pumped at asufficient rate). Furthermore, the controller typically receivesmultiple patient temperature inputs. The controller may adjust the heatexchanger and/or pump operation dynamically based on patient temperatureinformation and blood temperature information.

The bag-inlet temperature sensor 61 and the bag-outlet temperaturesensor 62 may be mounted permanently in the base unit 11 adjacent wherethe inlet and outlet of the bags are located. In order to improvethermal conductivity between the blood flowing within the bag and thetemperature sensors located outside of the bag—and thereby improve theaccuracy of the temperature readings—the bag may be provided with metalthermowells which extend into the flowpath of the blood at the bag'sinlet and outlet. When the bag is placed between the heating plates, thethermowells can accommodate and receive the temperature sensors 61, 62extending from the base unit 11. As discussed below, the metalthermowells can also be used as electrical conductors and thus be usedto detect leaks or air in the bag 21.

In the system shown in FIG. 6, a prime line 2021 may be provided tosupply a priming fluid (e.g., water) to the pod pumps. An airpurge/sample port 2019 may also be provided to facilitate air purgingand also to allow for sampling of the blood being returned to thepatient. A blood monitoring interface may also be provided, for example,including shunt sensor connections (mating luer locks) 2020 anddisposable H/S cuvette 2022 for a CDI™ Blood Parameter Monitoring System500 blood gas monitor sold by Terumo Cardiovascular Systems, Corp.

In various alternative embodiments, the controller 49 may detectabnormal conditions in the system based on several factors including:(i) the difference in the bag-inlet and bag-outlet temperatures measuredrespectively by the bag-inlet and bag-outlet sensors 61, 62, (ii) thevolumetric flow rate of blood through the disposable unit 16, and (iii)the power being provided to the base unit's heating plates. If each thepump pod 25 a, 25 b expels the same, known volume of blood during eachexpel stroke, the volumetric flow rate can be measured by simplymeasuring the rate of expel strokes, and multiplying that rate by volumeexpelled per stroke. (The flow rate can be determined in this way aslong as full pump strokes are being performed. As discussed above, thecontroller in a preferred embodiment monitors whether full strokes arebeing performed by dithering the valving mechanism and analyzing thepressure information from the actuation-chamber-pressure transducers.)The product of three factors—the measured flow rate, the measuredincrease in blood temperature, and the specific heat of the blood—shouldbe proportional to the power going into the heating plates. If thisproportion varies significantly during a procedure, the controllerpreferably generates an alarm signal, which may be used to cause anindication to a medical technician monitoring the procedure or which maybe used directly to stop the procedure.

Preferably, the controller generates two estimates based on a given setof temperature and flow-rate measurements, with one estimate based onall the uncertainties biased one way and the other estimate based on allthe uncertainties biased the other way. The electrical power beingconsumed by the heating plates should always be below one estimate andabove the other estimate; if the power measurement falls outside of thisrange, the controller will preferably generate the alarm signal.

It should be noted that the system may include other types of sensorsand systems. For example, the system could provide anticoagulant to thepatient, particularly to allow for extended treatments. The system couldprovide additional fluid to the patient, and may include a hydrationsensor to detect dehydration of the patient, particularly due to thehyperthermic treatment. The system could also include a hemolysis sensorto monitor for excessive amounts of hemolysis. Some of this sensing mayinvolve conductivity sensing using the thermal wells/sensors or othermechanisms.

3.1.7. Leak and Air Detection

In certain embodiments, detection of leaks in the heat-exchanger bag 21may be accomplished by measuring the electrical conductivity between oneor both of the thermowells 133 a, 133 b and one or both of the upper andlower heating plates 12, 14. As discussed above, the base unit 11includes sensors 61, 62 that interface with the thermowells 133 a, 133 bfor providing electrical connectivity between the base unit 11 and thedisposable unit 16. The base unit 11 typically also includes electricalprobes connected to each of the heating plates 12, 14, which should alsobe electrically conductive. If there is a leak, the electricalconductivity between the thermowells and the heating plates shouldincrease substantially (because the fluid passing through the leak isgenerally a much better conductor of electricity than the bag material).Normally, the resistance between the electrical probe contacting thethermowell and each of the electrical probes on the heating platesshould be quite high, because the plastic material from which the bag ismade is a relatively good insulator. However, if there is a leak, theliquid (e.g., the blood) passing through the leak in the bag provides avery good conductor of electricity, so the resistance dropssignificantly when there is a leak. Thus, the controller, which is incommunication with these electrical probes, measures the conductivitybetween the probes and generates an alarm signal when the conductivityincreases by a certain amount.

Similarly, the metal thermowells can also be used to detect air in theflow path in the bag. If there is air in the bag, the resistance betweenthe thermowells and the plates will increase, because air is a poorconductor of electricity. Thus, if the controller detects a decrease inthe electrical conductivity between the plates and the thermowells, andif the decrease is more than a certain amount, the controller willpreferably generate an error signal and will preferably cause theprocedure to stop.

Additionally or alternatively, the system could include other types ofsensors to detect leaks, e.g., a carbon dioxide sensor for detectingblood leakage. A carbon dioxide sensor would typically be placed in anappropriate location, such as proximate to the fluidic paths throughwhich blood passes, perhaps within a partially or fully enclosed space(e.g., within the heat exchanger with the door closed). The carbondioxide detector could be included in the base unit or otherwise incommunication with the base unit controller.

3.1.8. Patient Temperature Monitoring

In a blood-heating procedure, the temperature of the patient must beclosely monitored in order to prevent the patient from overheatingbeyond a safe limit. In certain embodiments, at least two separatetemperature probes are located in the patient, e.g., one in theabdomen—either in the bladder or the rectum, in contact with the bladderwall or the rectal wall—and the other through the nasal passage, incontact with back wall of the nasal passage (patient temperature can bemonitored using a single probe or more than two probes and can bemonitored from other locations or methods, e.g., by monitoring airexpired by the patient). If both sensors are properly positioned, thetemperature readings of the two probes should be within a certain range.If the temperature readings from the two probes differ from each othertoo much, the controller may generate an alarm signal and/or abort theprocedure. During the preparation for the blood-heating procedure, asthe probes are being inserted into the patient, the readings of the twoprobes may be compared with each other and also compared normal patienttemperature readings; when the two probes fall within a pre-set range ofeach other and within a range of normal patient temperature readings,the medical personnel positioning the probes will be able to tell whenthey have properly positioned the probes.

During the blood-heating procedure, the method shown in FIG. 19 ispreferably followed in order to ensure that the patient does not getdangerously overheated. In step 90, temperature readings from theabdominal and nasal probes are taken. In step 91, the readings arecompared with each other; if the readings fall outside of a pre-setrange, an alarm signal is generated indicating a fault in thetemperature readings. In step 92, the controller monitors thetemperature readings from one of the two probes and compares thosereadings to a pre-set upper limit; if a reading is above this pre-setupper limit, an alarm signal is generated indicating the patient isgetting too overheated.

As discussed above, the controller of the heat-exchanger system maymonitor patient body temperature using at least two temperature probes.In actuality, the controller really only needs temperature readings froma single temperature probe; the second temperature probe essentiallyprovides a control against which readings from the first temperatureprobe can be compared. In certain embodiments, then, a singletemperature probe may be used to provide patient temperature readings tothe controller. In such embodiments, an operator could independentlymonitor a second temperature probe and manually abort the procedure ifthe two temperature readings do not match sufficiently.

3.1.9. User Interface

FIG. 27 shows an exemplary user interface screen in accordance with anexemplary embodiment of the present invention. The right-hand side ofthe screen includes various therapy controls including (from top tobottom) indicators for the various therapy phases (i.e., system idle,pre-check, prime, warm-up, plateau, cool-down, and end-therapy) fordisplaying the current phase of treatment (in this example, “warm-up” ishighlighted, indicating that the therapy is currently in the warm-upphase), a phase progress indicator for showing, e.g., the time remainingor time elapsed in the current phase, and four control buttons throughwhich the operator can control the therapy (e.g., pause treatment, stoptreatment, start or re-start treatment, and step to the next phase). Itshould be noted that these four control buttons prevent an operator fromstepping backward to a previous stage. The left-hand side of the screenallows the operator to tab through screens providing patientinformation, status information, temperature graphs, flow graphs, andlogs.

3.1.10 Alternative Heat-Exchanger Embodiments

In the embodiments described above, fluid is heated or cooled by runningthe fluid through a heat-exchanger bag that is placed between two platesof a heat exchanger. Of course, the present invention is in no waylimited to the use of a heat-exchanger bag or plates. In alternativeembodiments, heat-exchanger bags may be used with other types of heatexchangers (e.g., a heat-exchanger bag could be rolled up and placed ina tubular chamber or could be placed in other types of heat exchangers,such as an oven, refrigerator, water bath, or radiator). Additionally oralternatively, other types of fluid conduits (e.g., a length of tubingand/or a radiator) may be used with one or more plates. The heatexchanger may include heating and/or cooling capabilities. In fact, theheat-exchanger could include both heating and cooling capabilities sothat the heat-exchanger system could be used for both heating andcooling applications, either as part of the same treatment (e.g., sothat blood could be heated for hyperthermic treatment and quicklyreturned to normal temperature following treatment) or as part ofseparate treatments (e.g., the base unit could be used to providehyperthermic treatment to one patient and later to provide hypothermictreatment to another patient).

In one particular alternative embodiment, the disposable unit includes,or is configured to use, a length of tubing as the heat-exchangercomponent. The length of tubing is preferably thin-walled lay-flattubing, although other types of tubing may be used. The tubing is placedin the radiator, which may be part of the disposable (e.g., the radiatormay be attached to the manifold so that the entire unit can be placed ina base unit), part of the base unit (e.g., the radiator may be integralor attached to one of the heat-exchanger plates), or a separatecomponent that may be disposable or reusable. In any case, the radiatorpreferably includes a channel for receiving the length of tubing.

FIG. 75 shows a radiator 8000 in accordance with an exemplary embodimentof the present invention. The radiator 8000 has a contiguous channelfrom a first opening 8001 to a second opening 8002. The channel isconfigured to receive a length of tubing 8006 (e.g., thin-walledlay-flat tubing) such that one end of the tubing will protrude from theopening 8001 and the other end of the tubing will protrude from theopening 8002, as shown in FIG. 76. The tubing may be placed in theradiator by the user (particularly if the radiator is part of the baseunit or is a separate, reusable component) or may be provided alreadyinstalled in the radiator (particularly if the radiator is part of thedisposable unit). The radiator is generally made of a thermallyconductive material, such as a thermally conductive plastic or metal. Inan exemplary embodiment, the radiator 8000 may be approximately sixinches in diameter and approximately two inches in height.

In this embodiment, the channel includes inner and outer concentricloops (8003 and 8004, respectively) that are connected via a serpentinesection 8005. Among other things, this configuration allows both of theopenings 8001, 8002 to be accessible along the outer edge of theradiator. Assuming the opening 8001 (leading to the inner loop 8003)represents the fluid inlet point and the opening 8002 (leading to theouter loop 8004) represents the fluid outlet point, then the fluid willflow through the tubing in the inner loop 8003 in a clockwise directionand will flow through the tubing in the outer loop 8004 in acounter-clockwise direction (using the orientation shown in FIG. 76).The serpentine section 8005 connects the two loops and reverses the flowdirection. It should be noted that the inner and outer loops 8003, 8004and the serpentine section 8005 are configured to avoid sharp or abruptfluid direction changes and therefore avoid imparting excessive shearforces or turbulence on the fluid. It should also be noted that thearrangement of tubing (and particularly lay-flat tubing, which expandswhen carrying pressurized fluid) and radiator should provide forefficient heat exchange because of the close coupling of the tubing withthe radiator and because of the large surface areas involved.

As discussed above, the radiator 8000 could be provided as part of thedisposable unit or as a separate component, and in such cases theradiator 8000 would generally be placed into an appropriately configuredheat exchanger of the base unit. For example, the radiator 8000 could beplaced between two plates of a heat exchanger (similar to the way theheat-exchanger bag is placed between two plates in various embodimentsdescribed above), in which case the heat exchanger may be configured toaccommodate the radiator 8000, such as, for example, by having the twoplates farther apart and/or using a special door hinge to allow theupper plate to lie flat against the top of the radiator. The bottomplate could include guides (e.g., guides 8007 as shown in FIG. 77 inboth top view and front view) or a cylindrical wall (e.g., cylindricalwall 8008 as shown in FIG. 78 in both top view and front view) tofacilitate placement of the radiator into the heat exchanger. Also asdiscussed above, the radiator could be part of the base unit. Forexample, the radiator 8000 could be integral to the bottom plate 14, asshown in FIG. 79.

Alternatively, certain types of radiators may be used without separatetubing, such that fluid is carried directly in the channel of theradiator. Such radiators would typically be disposable, although theycould be reusable, for example, after being rinsed and disinfected. FIG.80 shows an enclosed radiator 8009, similar to the radiator 8000described above, and including two ports 8010, 8011 for accommodatingfluid connections such as tubing connections to a manifold or directlyto one or more pumps. As with the radiator 8000 described above, theradiator 8009 could be part of the base unit, part of the disposableunit, or a separate component.

It should be noted that these embodiments are exemplary and are notintended to represent all of the types of heat-exchanger components thatcan be used in heat-exchanger systems of the types described herein.

3.2. Regional Hyperthermic Chemotherapy Treatment

FIG. 45 shows a representation of a regional hyperthermic chemotherapytreatment system 2600 in accordance with an exemplary embodiment of thepresent invention. The system 2600 is essentially a smaller version of aheat-exchanger system of the types described above in that it includes abase unit 2611 and a disposable unit 2601. Similar to the systemsdescribed above, the base unit 2611 includes a heat exchanger, apneumatic control system, a controller, and a built-in user interfacescreen 2606. The disposable 2601 (e.g., a cassette) includes two pumppods 2625 a and 2625 b, a single inlet 2602, a single outlet 2603, and adrug delivery interface 2604 (in this example, a syringe interface,although other types of interfaces, such as a luer port or a spike, maybe included in alternative embodiments).

An exemplary embodiment of the system 2600 is designed to circulateapproximately 1-2 liters per minute with added medication delivery, andalso provide for draining. The system 2600 may be used for regional orlocalized therapies, such as, for example, filling a body cavity (e.g.,upon removal of a tumor) with a chemotherapy solution at elevatedtemperature for some period of time, and then draining the cavity. Thesystem 2600 may also be used to locally circulate bodily fluid (e.g.,blood) with added medication, e.g., tourniquet a section of the body(e.g., a single lung) and circulate fluid.

In a typical application, the pump inlet 2602 may be in fluidcommunication with a fluid source (typically a separate reservoir,although fluid could be drawn directly from the patient), and the pumpoutlet 2603 may be in fluid communication with the patient fordelivering fluid from the fluid source to the patient. A fluid sourcereservoir or a separate receptacle may coupled so as to receive fluiddrained from the patient. Thus, for example, a reservoir may be used toprovide source fluid and a separate receptacle may be used to receivethe drained fluid or the same reservoir (which could be the patient) maybe used both to provide the source fluid and receive the drained fluid.The pump can be any fluid pump, including but not limited to, a pod pumpof the types described herein, or any other type of diaphragm or otherfluid pump. As fluid is pumped to the patient, medications or otherfluids (e.g., one or more chemotherapy drugs) may be introduced into thefluid through the drug delivery interface 2604, for example, using anautomatic syringe or any other automated or manual drug delivery device.

During such pumping, the temperature of the fluid is controlled and ismaintained at a predetermined temperature (e.g., about 37° C., or bodytemperature) during the entire process. The temperature control can beaccomplished by use of a temperature sensor in conjunction with aheater. In certain embodiments, the temperatures sensor may be any ofthe types described herein. The temperature sensor can be locatedanywhere in the fluid path, and in the preferred embodiment, is anywherein the fluid path outside of the patient. The fluid may be heated usingany method including, but not limited to, induction heating or surfaceheating. The fluid may be heated in the reservoir or somewhere elsealong the fluid path.

In one exemplary embodiment, the patient inlet may be located in thepatient's peritoneum. The fluid and drug may be pumped into the patientuntil either a threshold fluid pressure has been reached or until athreshold fluid volume has been pumped into the patient, signifyingcompletion of a fill stage. The fluid is typically allowed to remain inthe patient for a certain amount of time, after which it is typicallydrained from the patient (e.g., by actuating a variable impedance on thepatient outlet side). Fill/drain cycles may be repeated a predeterminednumber of times based on the patient's therapy needs.

In another exemplary embodiment, a portion of the patient (e.g., apatient's limb) may be isolated, e.g., using a tourniquet or pressurecuff. Bodily fluid (e.g., blood) mixed with medication or other fluidmay be circulated through the isolated area in a manner similar to thatdescribed above. The fluid temperature may be maintained using anin-line heater.

FIG. 84 shows a fluid circuit that may be used for providing regionalhyperthermic chemotherapy treatment, in accordance with an exemplaryembodiment of the present invention. A reservoir holds fluid to bedelivered to the patient. In this example, the fluid is pumped through aheater and into the patient. In alternative embodiments, the fluid maybe heated in the reservoir and the in-line heater may be omitted. Insome embodiments, the fluid in the reservoir may include medication,while in other embodiments, fluid may be added via the pump or by othermeans (e.g., a separate inlet into the fluid path. Fluid from thepatient may be drained back to the reservoir or to some other receptacle(or simply discarded). The volume of fluid pumped and/or drained may bemonitored in the reservoir, e.g., using a capacitive level probe orother sensor.

FIG. 85 shows another fluid circuit including a balancing chamber thatmay be used for providing regional hyperthermic chemotherapy treatment,in accordance with an exemplary embodiment of the present invention. Inthis example, fluid is heated in the reservoir, and the volume of fluidin the reservoir is monitored using a capacitive level probe. Fluid istypically pumped to the patient through the top balancing chamber byappropriate control the valves, although fluid may be pumped directly tothe patient (i.e., bypassing the balancing chamber) by appropriatecontrol of the valves. Fluid drained from the patient flows through thebottom balancing chamber back to the reservoir. The balancing chambershelp to maintain a constant volume of fluid into and out of the patient.

FIG. 86 shows another fluid circuit including a balancing chamber and asecond pump that may be used for providing regional hyperthermicchemotherapy treatment, in accordance with an exemplary embodiment ofthe present invention. In this example, the second pump is used to pumpfluid from the top balancing chamber to the patient, which also helps todrain fluid from the patient to the bottom balancing chamber. As inprevious embodiments, the fluid may be heated in the reservoir or in thefluid path.

FIG. 87 shows a fluid circuit including a drain valve that may be usedfor providing regional hyperthermic chemotherapy treatment, inaccordance with an exemplary embodiment of the present invention. Inthis example, the drain valve may be controlled to control the amount offluid entering and leaving the patient. For example, with the valveclosed, fluid may be pumped into the patient, e.g., to fill up a cavityof the patient. The drain valve may be partially or fully opened todrain the fluid from the patient or to allow for fluid circulationthrough the patient.

4. Thermal/Conductivity Sensors

Various embodiments of thermal and/or conductivity sensors aredescribed. Such thermal/conductivity sensors can be used in a widevariety of applications and are by no means limited tothermal/conductivity measurements of fluids or to thermal/conductivitymeasurements in the context of heat-exchanger systems.

4.1. Thermal Wells

In one exemplary embodiment, a thermal well is used to accommodate atemperature sensing probe. The thermal well comes into direct contactwith a subject media (e.g., a liquid such as blood) and the sensingprobe does not. Based on heat transfer dictated in large part by thethermodynamic properties of the thermal well and sensing probeconstruction, the sensing probe can determine the properties of thesubject media without coming into direct contact with the subject media.The accuracy and efficiency of the sensor apparatus arrangement dependson many factors including, but not limited to: construction material andgeometry of both the probe and the thermal well.

Referring now to FIGS. 50A and 50B, two embodiments of the sensorapparatus which includes the thermal well 5100 and the sensing probe5102, are shown in relation to a fluid line 5108. In these embodiments,the thermal well 5100 is integrated into the fluid line 5108. However,in other embodiment, some described below, the thermal well 5100 is notcompletely integrated into the fluid line 5108, i.e., the thermal well5100 can be made from different materials as compared with the fluidline 5108. In alternate embodiments, the thermal well 5100 is notintegrated into any fluid line but can be integrated into anything ornothing at all. For example, in some embodiments, the thermal well 5100can be integrated into a container, chamber, machine, protective sleeve,fluid pump, pump cassette, disposable unit, manifold, or other assembly,sub-assembly, or component. For purposes of the description, anexemplary embodiment is described for illustrative purposes. Theexemplary embodiment includes the embodiment where the thermal well 5100is in a fluid line. However, the sensor apparatus and the thermal wellcan be used outside of a fluid line.

Referring now to FIG. 50A, a side view showing a thermal well 5100formed in a fluid line 5108 which provides the space 5104 for subjectmedia to flow through, and a sensing probe 5102 is shown. Data from thesensing probe is transmitted using at least one lead 5106. An end viewof FIG. 50A is shown in FIG. 50B.

In this embodiment, the thermal well 5100 is one piece with the fluidline 5108. The total area of the thermal well 5100 can vary. By varyingthe geometry of the thermal well 5100, the variables, including, but notlimited to, the thermal conductivity characteristic of the thermal well5100 and thus, the heat transfer between the thermal well 5100 and thesensing probe 5102 will vary. As described in more detail below, thematerial construction of the thermal well 5100 is another variable inthe sensor apparatus. In some embodiments, the fluid line 5108 is madefrom a material having a desired thermal conductivity. This material mayvary depending on the purpose. The material can be anything including,but not limited to, any plastic, ceramic, metals or alloys of metals orcombinations thereof.

Referring now to FIGS. 51A and 51B, in these embodiments, the fluid line5108 and the thermal well 5100 are separate parts. In some embodiments,the fluid line 5108 and the thermal well 5100 are made form differentmaterials.

FIGS. 50A-50B and FIGS. 51A-51B show relatively simple embodiments ofthe sensor apparatus. Thus, for these embodiments, the sensing apparatusincludes a thermal well 5100 and a sensing probe 5102 where the thermalwell either is integrated as one continuous part with the fluid line5108 or is a separate part from the fluid line 5108. However, manyembodiments of the sensor apparatus are contemplated. Much of thevarious embodiments include variations on the materials and thegeometries of the thermal well 5100 and/or the sensing probe 5102. Thesevariations are dictated by multiple variables related to the intendeduse for the sensor apparatus. Thus, the subject media and theconstraints of the desired sensor, for example, the accuracy, time forresults and the fluid flow and subject media characteristics are but asampling of the various constraints that dictate the embodiment used. Inmost instances, each of the variables will affect at least one part ofthe embodiment of the sensor apparatus.

Thus, multiple variables affect the various embodiments of the sensorapparatus, these variables include but are not limited to: 1) geometryof the thermal well; 2) material composition of the thermal well; 3)material composition of the sensing probe; 4) desired flow rate of thesubject media; 5) length and width of the thermal well; 6) desiredaccuracy of the sensing probe; 7) wall thicknesses; 8) length and widthof the sensing probe; 9) cost of manufacture; 10) subject mediacomposition and characteristics including tolerance for turbulence; 11)geometry of sensing probe; and 12) desired speed of readings.

In the foregoing, various embodiments of the sensor apparatus aredescribed. The description is intended to provide information on theaffect the variables have on the sensor apparatus embodiment design.However, these are but exemplary embodiments. Many additionalembodiments are contemplated and can be easily designed based on theintended use of the sensor apparatus. Thus, by changing one or more ofthe above mentioned partial list of variables, the embodiment of thesensor apparatus may vary. Referring now to FIGS. 52A and 52B, twoembodiments of the thermal well 5100 are shown as different parts fromthe fluid line 5108. These embodiments show two geometries of thethermal well 5100. In FIG. 52A, the geometry includes a longer thermalwell 5100. In FIG. 52B, the thermal well 5100 geometry is shorter. Thelength and width of the thermal well 5100 produce varying properties andaccuracies of the thermal conductivity between the thermal well 5100 andthe sensing probe 5102. Depending on the use of the sensor apparatus,the thermal well 5100 geometry is one variable.

Referring now to FIG. 52A, the longer thermal well 5100 generallyprovides a greater isolation between the subject media temperature inthe fluid line 5104 and the ambient temperature. Although the longerthermal well 5100 geometry shown in FIG. 52A may be more accurate, theembodiment shown in FIG. 52B may be accurate enough for the purpose athand. Thus, the length and width of the thermal well 5100 can be anylength and width having the desired or tolerable accuracycharacteristics. It should be understood that two extremes of length areshown in these embodiments; however, any length is contemplated. Thedescription herein is meant to explain some of the effects of thevariables.

Still referring to FIGS. 52A and 52B, the longer thermal well 5100 shownin FIG. 52A may impact the fluid flow of the subject media in the fluidline 5108 to a greater degree than the embodiment shown in FIG. 52B. Itshould be understood that the length of the thermal well 5100 may alsoimpact the turbulence of the fluid flow. Thus, the length and width ofthe thermal well 5100 may be changed to have greater or lesser impact onthe fluid flow and turbulence of the fluid, while mitigating the othervariables.

The shape of the thermal well 5100 is also a variable. Any shape desiredis contemplated. However, the shape of the thermal well 5100, as withthe other variables, is determined in part based on the intended use ofthe sensor apparatus. For purposes of description, an exemplaryembodiment is described herein. However, the shape in the exemplaryembodiment is not meant to be limiting.

Referring now FIG. 53 for purposes of description, the thermal well 5100has been divided into 3 zones. The top zone 5402 communicates with thesensing probe (not shown); the middle zone 5404 provides the desiredlength of the thermal well 5100. As described above, the length maydictate the level of protrusion into the fluid path. The length isdictated in part by the desired performance characteristics as discussedabove. The middle zone 5404 also isolates the top zone 5402 from theambient. The middle zone 5404 may also serve to locate, fasten or sealthe thermal well 5100 into the fluid line (shown as 5108 in FIGS.50A-50B).

The bottom zone 5406, which in some embodiments may not be necessary(see FIG. 56K) thus, in these embodiments, the middle zone 5404 and thebottom zone 5406 may be a single zone. However, in the exemplaryembodiment, the bottom zone 5406 is shaped to aid in press fitting thethermal well into an area in the fluid line and may locate and/or fastenthe thermal well 5100 into the fluid line 5108. In other embodiments,zone 5406 may be formed to facilitate various joining methods (see FIGS.56A-56J, 56L-56S) Referring now to FIG. 54 a cross section of theexemplary embodiment of the thermal well 5100 is shown. The dimensionsof the exemplary embodiment of the thermal well 5100 include a length Aof approximately 0.113 inches (with a range from 0-0.379 inches), aradius B of approximately 0.066 inches and a wall thickness C rangingfrom approximately 0.003-0.009 inches. These dimensions are given forpurposes of an exemplary embodiment only. Depending on the variables andthe intended use of the sensing apparatus, the thermal well 5100dimensions may vary, and the various embodiments are not necessarilyproportional.

In some embodiments, the wall thickness can be variable, i.e., the wallthickness varies in different locations of the thermal well. Althoughthese embodiments are shown with variable thicknesses in variouslocations, this is for description purposes only. Various embodiments ofthe thermal well may incorporate varying wall thickness in response tovariables, these varying wall thicknesses can be “mixed and matched”depending on the desired properties of the sensing apparatus. Thus, forexample, in some embodiments, a thinner zone 5404 may be used withthinner zone 5406 and vice-versa. Or, any other combination of “thinner”and “thicker” may be used. Also, the terms used to describe the wallthicknesses are relative. Any thickness desired is contemplated. Thefigures shown are therefore for descriptive purposes and represent twoembodiments where many more are contemplated.

Referring now to FIGS. 55A and 55B, zone 5402 can be thicker or thinneras desired. The thinner zone 5402, amongst other variables, generallyprovides for a faster sensing time while a thicker zone may be usefulfor harsh environments or where sensor damping is desired. Zone 5404 maybe thicker, amongst other variables, for greater strength or thinnerfor, amongst other variables, greater isolation from ambient. Zone 5406can be thinner or thicker depending on the fastening method used.

The thermal well 5100, in practice, can be embedded into a fluid line5108, as a separate part from the fluid line 5108. This is shown anddescribed above with respect to FIGS. 51A-51B. Various embodiments maybe used for embedding the thermal well 5100 into the fluid line 5108.Although the preferred embodiments are described here, any method orprocess for embedding a thermal well 5100 into a fluid line 5108 can beused. Referring now to FIGS. 56A-56S, various configurations forembedding the thermal well 5100 into the fluid line 5108 are shown. Forthese embodiments, the thermal well 5100 can be made from any materials,including but not limited to, plastic, metal, ceramic or a combinationthereof. The material may depend in some part on the compatibility withthe intended subject media. The fluid line 5108, in these embodiments,may be made from plastic, metal, or any other material that iscompatible with the subject media.

Referring first to FIG. 56A, the thermal well 5100 is shown press fitinto the fluid line 5108 using the zone 5404 (shown in FIG. 53). In FIG.56B, the thermal well 5100 is shown press fit into the fluid line 5108using the zone 5406. Referring now to FIG. 56C, the thermal well 5100 isshown retained in the fluid line 5108 with flexible tabs 5704, an O-ringis also provided. Referring now to FIG. 56D, the thermal well 5100 isshown inserted into the fluid line 5108 with an O-ring 5702. The thermalwell 5100 is also shown as an alternate embodiment, where the thermalwell 5100 zone 5406 includes an O-ring groove. The O-ring groove can becut, formed, spun, cast or injection molded into the thermal well, orformed into the thermal well 5100 by any other method. FIG. 56E shows asimilar embodiment to that shown in FIG. 56D, however, the O-ring grooveis formed in zone 5406 rather than cut, molded or cast as shown in FIG.56D. Referring now to FIG. 56F, the thermal well 5100 is shown press fitinto the fluid line 5108, zone 5406 includes flexibility allowing theedge of zone 5406 to deform the material of the fluid line 5108.Referring now to FIG. 56G, the thermal well 5100 includes cuts 5706 onthe zone 5406 providing flexibility of the zone 5406 for assembly withthe fluid line 5108. An O-ring 5702 is also provided. Although two cutsare shown, a greater number or less cuts are used in alternateembodiments.

Referring now to FIG. 56H, the embodiment shown in FIG. 56F is shownwith the addition of an O-ring 5702. Referring to FIG. 561, the thermalwell 5100 is shown insert molded in the fluid line 5108. Zone 5406 isformed to facilitate or enable assembly by insert molding.

FIG. 56J shows an embodiment where the thermal well 5100 is heat staked5708 to retain the thermal well 5100 in the fluid line 5108. In someembodiments of FIG. 56J, an O-ring 5710 is also included. In thisembodiment, the O-ring 5710 has a rectangular cross section. However, inalternate embodiments, the O-ring may have a round or X-shaped crosssection. Likewise, in the various embodiments described herein having anO-ring, the O-ring in those embodiments can have a round, rectangular orX-shaped cross section, or any cross sectional shape desired.

Referring now to FIG. 56K, the thermal well 5100 is retained in thefluid line 5108 by adhesive 5712. The adhesive can be any adhesive, butin one embodiment, the adhesive is a UV curing adhesive. In alternateembodiments, the adhesive may be any adhesive that is compatible withthe subject media. In this embodiment, the thermal well 5100 is shownwithout a zone 5406.

Referring now to FIG. 56L, thermal well 5100 is shown ultrasonicallywelded in the fluid line 5108. The zone 5406 is fabricated to enablejoining by ultrasonic welding. Referring now to FIG. 56M, a thermal well5100 is shown insert molded in the fluid line 5108. Zone 5406 is aflange for the plastic in the fluid line 5108 to flow around. In theembodiment shown, the flange is flat, however, in other embodiments; theflange may be bell shaped or otherwise.

Referring now to FIG. 56N, the thermal well 5100 is shown retained inthe fluid line 5108 by a retaining plate 5714 and a fastener 5716.O-ring 5702 is also shown. Referring now to FIGS. 560-56P, an end viewis shown of a thermal well 5100 that is retained in a fluid line 5108 bya retaining ring 5718 (FIG. 560) or in an alternate embodiment, a clip5720 (FIG. 56P). O-ring 5702 is also shown. Referring now to FIG. 56Q,the embodiment of FIG. 56C is shown with an alternate embodiment of thethermal well 5100. In this embodiment of the thermal well 5100 thereferred to as zone 5404 in FIG. 53 includes a taper that may allow foreasier alignment with a sensing probe, better isolation of zone 5402from the ambient and better flow characteristics in the fluid path. Thethermal well 5100 is shown retained in the fluid line 5108 usingflexible tabs 5704. An O-ring is also provided.

FIG. 56R shows the embodiment of FIG. 56J with an alternate embodimentof the thermal well 5100. The thermal well 5100 shown in this embodimenthas a taper in zone 5404 that may allow for easier alignment with asensing probe, may allow better isolation of zone 5402 from the ambientand may allow better flow characteristics in the fluid path. Zone 5402provides a hemispherical contact for effective thermal coupling with athermal probe. The thermal well 5100 is heat staked 5708 to retain thethermal well 5100 in the fluid line 5108. In some embodiments of FIG.56R, an O-ring 5710 is also included. In this embodiment, the O-ring5710 has a rectangular cross section. However, in alternate embodiments,the O-ring can have a round or X-shaped cross section.

Referring now to FIG. 56S, the embodiment of FIG. 56H is shown with analternate embodiment of the thermal well 5100. FIG. 56S is shown withthe addition of an O-ring 5702. In this embodiment of the thermal well5100 zone 5404 (as shown in FIG. 53) has convolutions that may allowbetter isolation of zone 5402 from the ambient. While several geometrieshave been shown for zone 5404, many others could be shown to achievedesired performance characteristics.

4.2. Sensing Probes

Referring now to FIG. 57, a sectional view of an exemplary embodiment ofthe sensing probe 5800 is shown. The housing 5804 is a hollow structurethat attaches to the tip 5802. The tip is made of a highly thermallyconductive material. The housing 5804, in the exemplary embodiment, ismade from a thermally insulative material. In some embodiments, thehousing is made of a thermally and electrically insulative material. Inthe exemplary embodiment, the housing 5804 is made of plastic which is athermally insulative and electrically insulative material. The tip 5802either contacts the subject media directly, or else is mated with athermal well.

In the exemplary embodiment, the tip 5802 is attached to the housing5804 using a urethane resin or another thermal insulator in between(area 5807) the tip 5802 and the housing 5804. Urethane resinadditionally adds structural support. In alternate embodiments, otherfabrication and joining methods can be used to join the tip 5802 to thehousing 5804.

The tip 5802 of the sensing probe 5800 is made of a thermally conductivematerial. The better thermally conductive materials, for example,copper, silver and steel, can be used, however, depending on the desireduse for the sensing probe and the subject media; the materials may beselected to be durable and compatible for the intended use.Additionally, factors such as cost and ease of manufacture may dictate adifferent material selection. In one exemplary embodiment, the tip 5802is made from copper. In other embodiments, the material can be an alloyof copper or silver, or either solid or an alloy of any thermallyconductive material or element, including but not limited to metals andceramics. However, in the exemplary embodiments, the tip 5802 is madefrom metal.

In the exemplary embodiment, the tip 5802 is shaped to couple thermallywith a thermal well as described in the exemplary embodiment of thethermal well above. In the exemplary embodiment as well as in otherembodiments, the tip 5802 may be shaped to insulate the thermal sensor5808 from the ambient. In the exemplary embodiment, the tip 5802 is madefrom metal.

In alternate embodiments a non-electrically conductive material is usedfor the tip. These embodiments may be preferred for use where it isnecessary to electrically insulate the thermal well from the probe. Inanother alternate embodiment, the tip 5802 may be made from anythermally conductive ceramic.

In the exemplary embodiment, the thermal sensor 5808 is located in thehousing and is attached to the interior of the tip 5802 with a thermallyconductive epoxy 5812. In the exemplary embodiment, the epoxy used isTHERMALBOND, however, in other embodiments; any thermal grade epoxy canbe used. However, in alternate embodiments, a thermal grease may beused. In alternate embodiments, an epoxy or grease is not used.

The thermal sensor 5808, in the exemplary embodiment, is a thermistor.The thermistor generally is a highly accurate embodiment. However inalternate embodiments, the thermal sensor 5808 can be a thermocouple orany other temperature sensing device. The choice of thermal sensor 5808may again relate to the intended use of the sensing apparatus.

Leads 5814 from the thermal sensor 5808 exit the back of the housing5804. These leads 5814 attach to other equipment used for calculations.In the exemplary embodiment, a third lead 5816 from the tip 5802 is alsoincluded. This third lead 5816 is attached to the tip on a tab 5818. Thethird lead 5816 is attached to the tip 5802 because in this embodiment,the tip 5802 is metal and the housing is plastic. In alternateembodiments, the housing 5804 is metal, thus the third lead 5816 may beattached to the housing 5804. Thus, the tip 5802, in the exemplaryembodiment, includes a tab 5818 for attachment to a lead. However, inalternate embodiments, and perhaps depending on the intended use of thesensing apparatus, the third lead 5816 may not be included. Also, inalternate embodiments where a third lead is not desired, the tip 5802may not include the tab 5818. Referring now to FIG. 58, an exploded viewof the sensing probe 5800 is shown.

Referring now to FIG. 59 an alternate embodiment of the exemplaryembodiment is shown. In this embodiment, the tip 6002 of the sensingprobe is shown. The tip 6002 includes a zone 6004 that will contacteither a subject media to be tested or a thermal well. A zone 6006attaches to the sensor probe housing (not shown). An interior area 6008accommodates the thermal sensor (not shown). In this embodiment, the tip6002 is made from stainless steel. However, in other embodiments, thetip 6002 can be made from any thermally conductive material, includingbut not limited to: metals (including copper, silver, steel andstainless steel), ceramics or plastics.

In the exemplary embodiment, zone 6006 includes a tab 6010. A third lead(as described with respect to FIG. 57, 5816) attaches from the tab 6010.Referring next to FIGS. 60A and 60B, the sensing probe 6000 is shownincluding the tip 6002 and the housing 6012. In one embodiment, thehousing 6012 is made from any thermally insulative material, includingbut not limited to, plastic. In one embodiment, the housing 6012 ispress fit to the tip 6002, glued or attached by any other method. In oneembodiment, the thermal sensor 6014 is thermally coupled to the tip 6002with thermal grade epoxy or, in alternate embodiments, thermal grease6022. Two leads 6016 from the thermal sensor 6014 extend to the distalend of the housing. In some embodiments, a third lead 6018 is attachedto the tip 6002 from the tab 6010. As discussed above, in someembodiments where the third lead is not desired, the tip 6002 does notinclude a tab 6010.

Referring now to FIG. 60B, an alternate embodiment of the sensing probe6000 is shown. In this embodiment, the housing 6012 is a plastic moldedover zone 6006 of the tip 6002 and the leads 6016, and in someembodiments, a third lead 6018.

Referring now to FIG. 61, a full side view of one embodiment of thesensing probe 6000 shown in FIGS. 59-60B is shown. The sensing probe6000 includes a housing 6012, a tip 6002 and the leads 6016, 6018.Flange 6020 is shown. In some embodiment, flange 6020 is used to mountand/or attachment to equipment.

Referring now to FIG. 62A, the sensing probe 6000 shown in FIGS. 59-61,is shown coupled to a thermal well 5100 which is fastened into a fluidline 5108. In the embodiment as shown, two leads 6016 are shown at thedistal end of the sensing probe 6000. And, in some embodiments, a thirdlead 6018 is also incorporated into the sensing probe 6000. FIG. 62Bshows an alternate embodiment where the sensing probe 6000 includes twoleads 6016 but does not include the third lead 6018.

Referring now to both FIGS. 62A and 62B, the tip 6002 of the sensingprobe 6000 is in direct contact with the thermal well 5100. Referringback to FIG. 53 and still referring to FIG. 62A and 62B the thermal well5100 includes a zone 5402. The thermal well 5100 is hollow, and theinner part of zone 5402 is formed such that it will be in mating contactwith the sensing probe tip 6002. As shown in this embodiment, thethermal well 5100 is designed to have a mating geometry with the sensingprobe 6000. Thus, the geometry of the thermal well 5100 may depend onthe geometry of the tip 6002 of the sensing probe 6000 and vice-versa.In some embodiments, it may be desirable that the sensing probe 6000does not have a tight fit or a perfect mate with the thermal well 5100.

Referring now to FIG. 63A, one embodiment of the sensing probe 5800 (asshown in FIG. 57) is shown coupled to a thermal well 5100 which isfastened into a fluid line 5108. In the embodiment as shown, two leads5814 are shown at the distal end of the sensing probe 5800. In someembodiments, a third lead 5816 is also incorporated into the sensingprobe 5800. FIG. 63B shows an alternate embodiment where the sensingprobe 5800 includes two leads 5814 but does not include the third lead5816.

Referring now to both FIGS. 63A and 63B, the tip 5802 of the sensingprobe 5800 is in direct contact with the thermal well 5100. Referringback to FIG. 53 and still referring to FIGS. 63A and 63B, the thermalwell 5100 includes a zone 5402. The thermal well 5100 is hollow, and theinner part of zone 5402 is formed such that it will be in mating contactwith the sensing probe tip 5802. As shown in this embodiment, thethermal well 5100 is designed to have a mating geometry with the sensingprobe 5800. Thus, the geometry of the thermal well 5100 depends on thegeometry of the tip 5802 of the sensing probe 5800 and vice-versa.

4.3. Sensor Apparatus

For purposes of description of the sensor apparatus, the sensorapparatus is described with respect to exemplary embodiments. Theexemplary embodiments are shown in FIGS. 62A, 62B, and FIG. 64, withalternate exemplary embodiments in 63A and 63B. In alternate embodimentsof the sensor apparatus, the sensing probe can be used outside of thethermal well. However, the sensor apparatus has already been describedherein alone. Thus, the description that follows describes oneembodiment of the exemplary embodiment of the sensor apparatus whichincludes, for this purpose, a sensing probe and a thermal well.

Referring now to FIG. 64, in an exemplary embodiment, the sensing probe6000 shown in FIG. 62A and the thermal well 5100 are shown coupled andoutside of a fluid line. As described above, the thermal well 5100 canbe in a fluid line, a protective sleeve, any disposable, machine,chamber, cassette or container. However, for purposes of thisdescription of the exemplary embodiment, the thermal well 5100 is takento be anywhere where it is used to determine thermal and/or conductiveproperties (FIG. 62A) of a subject media.

A subject media is in contact with the outside of zone 5402 of thethermal well 5100. Thermal energy is transferred from the subject mediato the thermal well 5100 and further transferred to the tip 6002 of thesensing probe 6000. Thermal energy is then conducted to the thermalsensor 6014. The thermal sensor 6014 communicates via leads 6016 withequipment that can determine the temperature of the subject media basedon feedback of the thermal sensor 6014. In embodiments whereconductivity sensing is also desired, lead 6018 communicates withequipment that can determine the conductivity of the subject media. Withrespect to determining the conductivity of the subject media, inaddition to the lead 6018, a second electrical lead/contact (not shown)would also be used. The second lead could be a second sensor apparatusas shown in FIG. 64, or, alternatively, a second probe that is notnecessarily the same as the sensor apparatus shown in FIG. 64, butrather, any probe or apparatus capable of sensing capacitance of thesubject media, including, an electrical contact.

Heat transfer from the tip 6002 to the thermal sensor 6014 may beimproved by the use of a thermal epoxy or thermal grease 6022.

Referring now to FIGS. 63A and 63B, in the alternate exemplaryembodiment, whilst the sensing probe 5800 is coupled to the thermal well5100, the tip 5802, having the geometry shown, forms an air gap 6402between the inner zones 5404 and 5406 of the thermal well 5100 and thetip 5802. The air gap 6402 provides an insulative barrier so that onlythe top of the sensing tip of 5802 is in communication with the top zone5402 of the thermal well 5100.

The sensing probe 5800 and thermal well 5100 are shown coupled andoutside of a fluid line. As described above, the thermal well 5100 canbe in a fluid line, a protective sleeve, disposable unit, machine,non-disposable unit, chamber, cassette or container. However, forpurposes of this description of the exemplary embodiment, the thermalwell 5100 is taken to be anywhere where it is used to determine thermaland/or conductive properties (FIG. 63A) of a subject media.

A subject media is in contact with the outside of zone 5402 of thethermal well 5100. Thermal energy is transferred from the subject mediato the thermal well 5100 and further transferred to the tip 5802 of thesensing probe 5800. Thermal energy is then conducted to the thermalsensor 5808. The thermal sensor 5808 communicates via leads 5814 withequipment that can determine the temperature of the subject media basedon feedback of the thermal sensor 5808. In embodiments whereconductivity sensing is also desired, lead 5816 communicates withequipment that can determine the conductivity of the subject media. Withrespect to determining the conductivity of the subject media, inaddition to the lead 5816, a second electrical lead (not shown) wouldalso be used. The second lead could be a second sensor apparatus asshown in FIG. 63A, or, alternatively, a second probe that is notnecessarily the same as the sensor apparatus shown in FIG. 63A, butrather, any probe or apparatus capable of sensing capacitance of thesubject media, including, an electrical contact.

Heat transfer from the tip 5802 to the thermal sensor 5808 can beimproved by the use of a thermal epoxy or thermal grease 5812.

Referring now to FIG. 65, an alternate embodiment showing a sensingprobe 6602 coupled to a thermal well 5100 is shown. For purposes of thisdescription, any embodiment of the sensing probe 6602 and any embodimentof the thermal well 5100 can be used. In this embodiment, to increasethe thermal coupling between the tip of the sensing probe 6602 and thethermal well 5100, thermal grease 6604 is present at the interface ofthe tip of the sensing probe 6602 and the inner zone 5402 of the thermalwell 5100. In one embodiment, the amount of thermal grease 6604 is avolume sufficient to only be present in zone 5402. However, in alternateembodiments, larger or smaller volumes of thermal grease can be used.

4.4. Sensor Apparatus Systems

Referring now to FIG. 66, a sensor apparatus system is shown. In thesystem, the sensor apparatus is shown in a device containing a fluidline 5108. The sensor apparatus includes the sensing probe 6000 and thethermal well 5100. In this embodiment, the thermal well 5100 and fluidline 5108 is a disposable portion and the sensing probe 6000 is areusable portion. Also in the reusable portion is a spring 6700. Thespring 6700 and sensing probe 6000 are located in a housing 6708. Thehousing 6708 can be in any machine, container, device or otherwise. Thespring 6700 can be a conical, a coil spring, wave spring, or urethanespring.

In this embodiment, the thermal well 5100 and the sensing probe 6000 mayinclude alignment features 6702, 6704 that aid in the thermal well 5100and sensing probe 6000 being aligned. The correct orientation of thethermal well 5100 and the sensing probe 6000 may aid in the mating ofthe thermal well 5100 and the sensing probe 6000 to occur. Theconfiguration of the space 6706 provides the sensing probe 6000 withspace for lateral movement. This allows the sensing probe 6000 to, ifnecessary; move laterally in order to align with the thermal well 5100for mating.

The sensing probe 6000 is suspended by a spring 6700 supported by theflange 6020. The spring 6700 allow vertical movement of the sensingprobe 6000 when the thermal well 5100 mates with the sensing probe 6000.The spring 6700 aids in establishing full contact of the sensing probe6000 and the thermal well 5100. The fluid line 5108 can be in anymachine, container, device or otherwise. The fluid line 5108 contains afluid path 5104. A subject media flows through the fluid path 5104 andthe thermal well 5100, located in the fluid line 5108 such that thethermal well 5100 has ample contact with the fluid path 5104 and cansense the temperature properties and, in some embodiments, theconductive properties of the subject media. The location of the thermalwell 5100 in the fluid path 5104, as described in more detail above, maybe related to the desired accuracy, the subject media and otherconsiderations.

The spring 6700 and sensing probe 6000 assembly, together with the space6706 in the housing 6708 may aid in alignment for the mating of thesensing probe 6000 and the thermal well 5100. The mating provides thethermal contact so that the thermal well 5100 and the sensing probe 6000are thermally coupled.

A wire 6710 is shown. The wire contains the leads. In some embodiments,there are two leads. Some of these embodiments are temperature sensing.In other embodiments, the wire contains three or more leads. Some ofthese embodiments are for temperature and conductivity sensing.

Referring now to FIG. 67, an alternate embodiment of the system shown inFIG. 66 is shown. In this embodiment, the sensing probe 6000 issuspended by a coil spring 6800. A retaining plate 6802 captures thecoil spring 6800 to retain the spring 6800 and sensing probe 6000. Inone embodiment, the retaining plate 6802 is attached to the housing 6708using screws. However, in alternate embodiments, the retaining plate6802 is attached to the housing 6708 using any fastening methodincluding but not limited to: adhesive, flexible tabs, press fit, andultrasonic welding. Aligning features 6806 on the housing 6708 aid inalignment of the sensing probe 6000 to a thermal well (not shown).Lateral movement of the sensing probe 6000 is provided for by clearancein areas 6808 in the housing 6708. A wire 6710 is shown. The wirecontains the leads. In some embodiments, there are two leads. Some ofthese embodiments are temperature sensing. In other embodiments, thewire contains three or more leads. Some of these embodiments are fortemperature and conductivity sensing.

Referring now to FIG. 68, a sensing probe 6000 is shown in a housing6708. In these embodiments, an alternate embodiment of a spring, aflexible member 6900, is integrated with the sensing probe 6000 to allowvertical movement of the sensing probe 6000 within the housing 6708. Aretaining plate 6902 captures the flexible member 6900 to retain theflexible member 6900 and sensing probe 6000. In one embodiment, theretaining plate 6902 is attached to the housing 6708 using screws.However, in alternate embodiments, the retaining plate 6902 is attachedto the housing 6708 using any fastening method including but not limitedto: adhesive, flexible tabs, press fit, and ultrasonic welding. Lateralmovement of the sensing probe 6000 is provided for by clearance in areas6908 in the housing 6708. A wire 6710 is shown. The wire contains theleads. In some embodiments, there are two leads. Some of theseembodiments are temperature sensing. In other embodiments, the wirecontains three or more leads. Some of these embodiments are fortemperature and conductivity sensing.

Referring now to FIG. 69, an alternate embodiment of a sensing probe6000 in a housing 7002 is shown. In this embodiment, flexible member7000 is attached or part of the housing 7002, provides for verticalmovement of the sensing probe 6000. In this embodiment, the openings7004, 7006 in housing 7002 are sized such that the sensing probe 6000experiences limited lateral movement. Flexible member 7000 acts on theflange 7008 on the sensing probe 6000. A wire 6710 is shown. The wirecontains the leads. In some embodiments, there are two leads. Some ofthese embodiments are temperature sensing. In other embodiments, thewire contains three or more leads. Some of these embodiments are fortemperature and conductivity sensing.

The flange, as shown and described with respect to FIGS. 61, 66, 69, canbe located in any area desired on the sensing probe 6000. In otherembodiments, the sensing probe may be aligned and positioned by otherhousing configurations. Thus, the embodiments of the housing shownherein are only some embodiments of housings in which the sensorapparatus can be used. The sensor apparatus generally depends on beinglocated amply with respect to the subject media. The configurations thataccomplish this can vary depending on the subject media and the intendeduse of the sensing apparatus. Further, in some embodiments where thethermal well is not used, but rather, the sensing probe is used only,the housing configurations may vary as well.

The sensing apparatus, in some embodiments, is used to senseconductivity. In some embodiments, this is in addition to temperaturesensing. In those embodiments where both temperature and conductivitysensing is desired, the sensing probe typically includes at least threeleads, where two of these leads may be used for temperature sensing andthe third used for conductivity sensing.

Referring now to FIG. 70, for conductivity sensing, at least two sensors7102, 7104 are located in an area containing the subject media. In theembodiment shown, the area containing the subject media is a fluid path5104 inside a fluid line 5108. The conductivity sensors 7102, 7104 canbe one of the various embodiments of sensing probes as described above,or one of the embodiments of the sensor apparatus embodiments (includingthe thermal well) as described above. However, in other embodiments,only one of the sensors is one of the embodiments of the sensorapparatus or one of the embodiments of the sensing probe, and the secondsensor is any electrical sensor known in the art. Thus, in the systemsdescribed herein, conductivity and temperature can be sensed throughusing either one of the sensor apparatus or one of the sensor probes asdescribed herein and a second capacitance sensor, or one of the sensorapparatus or one of the sensor probes as described herein and anelectrical sensor.

Referring now to FIG. 71, an alternate embodiment of a sensor apparatusincluding a sensing probe 7200 and a thermal well 5100 is shown in afluid line 5108. In this embodiment, the sensing probe 7200 isconstructed of a metal housing. The thermal well 5100 is alsoconstructed of metal. The thermal well 5100 and the sensing probe 7200can be made from the same metal or a different metal. The metal, in thepreferred embodiment, is a conductive metal, which may include stainlesssteel, steel, copper and silver. A lead 7202 is attached to the sensingprobe 7200 housing for conductivity sensing. The thermal sensing leads7204 are attached to a thermal sensor located inside the sensing probe7200 housing. In this embodiment, therefore, the third lead 7202 (or thelead for conductivity sensing) can be attached anywhere on the sensingprobe 7200 because the sensing probe 7200 is constructed of metal. Inthe previously described embodiments, where the sensing probe housingwas constructed of plastic, and the sensing tip constructed of metal,the third lead for conductivity sensing was attached to the sensing tip.

A known volume of subject media may be used to determine conductivity.Thus, two sensors may be used and the volume of fluid between the twosensors can be determined. Conductivity sensing is done with the twoelectrical contacts (as described above), where one or both can be thesensor apparatus. The volume of subject media between the two contactsis known.

Conductivity sensing is done by determining the conductivity from eachof the sensors and then determining the difference. If the difference isabove a predetermined threshold, indicating an abnormal difference inconductivity between the first and second sensor (the designations“first” and “second” being arbitrary), then it can be inferred that airmay be trapped in the subject media and a bubble detection alarm may begenerated to indicate a bubble. Thus, if there is a large decrease inconductivity (and likewise, a large increase in resistance) between thefirst and second sensor, air could be trapped and bubble presence may bedetected.

Leaks in a machine, system, device or container may be determined usingthe conductivity sensing. Where a sensing apparatus is in a machine,device or system, and that sensing apparatus senses conductivity, in oneembodiment, a lead from the sensor apparatus (or electrical contacts) toan analyzer or computer machine may be present. In some embodiments, theanalyzer that analyzes the electrical signals between the contacts isconnected to the metal of the machine, device, system or container. Ifthe analyzer senses an electrical signal from the machine, then a fluidleak may be inferred.

For the various embodiments described herein, a fluid line can be madeof any material including metal and plastic. In most embodiments, thefluid line is compatible with the subject media and has the desiredcharacteristics depending on the configuration of the thermal well inthe fluid line. The fluid line can be part of a disposable unit thatattaches to the sensor apparatus. In some of these embodiments, thefluid line includes the thermal well. The subject media is locatedinside the fluid line and the sensing probe provides sensing dataregarding the subject media once the sensing probe and thermal well areamply mated.

The fluid line can be a chamber, a hose, a fluid path or other space orconduit for holding a volume of subject media. In some embodiments, thefluid line is a designed to hold fluid having a flow rate. In otherembodiments, the space is designed to hold mostly stagnant media ormedia held in the conduit even if the media has flow.

In some embodiments, the sensor apparatus may be used based on a need toseparate the subject media from the sensing probe. However, in otherembodiments, the sensing probe is used for temperature and/orconductivity sensing directly with subject media.

In some embodiments, the thermal well may be part of a disposableportion of a device, machine, system or container. Thus, the thermalwell may be in direct contact with subject media and may be the onlycomponent that is contaminated by same. In these embodiments, thesensing probe may be part of a machine, device, system or container, andbe disposable or non-disposable.

5. Conclusion

Various types and configurations of pump pods, heat-exchanger systems,and thermal/conductivity sensors are described above. It should be notedthat a wide variety of embodiments can be produced from variouscombinations of components. For example, certain heat-exchanger systemsmay be configured without pump pods or thermal/conductivity sensors, maybe configured with pump pods but not thermal/conductivity sensors, ormay be configured with thermal/conductivity sensors but not pump pods.Pump pods can be used in a wide variety of applications and are by nomeans limited to use in heat-exchanger systems or for pumping of bodilyfluids or medical fluids. Thermal/conductivity sensors can be used in awide variety of applications and are by no means limited tothermal/conductivity measurements of fluids or to thermal/conductivitymeasurements in the context of heat-exchanger systems.

Various embodiments are described above with reference to pneumaticactuation systems, specifically for operating pod pumps. It should benoted, however, that pod pumps can be operated using other types ofcontrol fluids, such as, for example, hydraulic fluids, in which casethe actuation system would typically include an appropriate controlfluid delivery system for delivering control fluid under positive and/ornegative pressures. Thus, for example, a heat-exchanger system couldinclude a hydraulic actuation system rather than a pneumatic actuationsystem, in which case pressurized hydraulic fluid could be stored in oneor more reservoirs or be provided using other pressurizing means (e.g.,a hydraulic fluid pump).

Although the above discussion discloses various exemplary embodiments ofthe invention, it should be apparent that those skilled in the art canmake various modifications that will achieve some of the advantages ofthe invention without departing from the true scope of the invention.

1. A method for heating or cooling a fluid, the method comprising:providing at least one reciprocating positive-displacement pump, eachpump having: a curved rigid chamber wall; a flexible membrane attachedto the rigid chamber wall, so that the flexible membrane and rigidchamber wall define a pumping chamber; an inlet for directing fluidthrough the rigid chamber wall into the pumping chamber in at least oneof (a) a direction that is substantially tangential to the rigid chamberwall and (b) a direction that provides low-shear flow into the pumpingchamber; and an outlet for directing fluid through the rigid chamberwall out of the pumping chamber in at least one of (a) a direction thatis substantially tangential to the rigid chamber wall and (b) adirection that provides low-shear flow out of the pumping chamber;providing a heat exchanger; and pumping the fluid from at least onesource using the at least one reciprocating positive-displacement pumpso as to cause the fluid to pass through the heat exchanger.
 2. A methodaccording to claim 1, wherein each pump is provided with a rigid chamberwall that is hemispheroid.
 3. A method according to claim 1, whereineach pump is provided with a rigid limit structure for limiting movementof the membrane and limiting the maximum volume of the pumping chamberthe flexible membrane and the rigid limit structure defining anactuation chamber.
 4. A method according to claim 3, wherein each pumpis provided with a rigid chamber wall that is hemispheroid and a rigidlimit structure that is hemispheroid such that the pumping chamber isspheroid when the membrane is urged against the rigid limit structure,and the actuation chamber is spheroid when the membrane is urged againstthe rigid chamber wall.
 5. A method according to claim 1, whereinproviding the at least one reciprocating positive-displacement pumpcomprising: providing a pair of reciprocating, positive-displacementpumps as in any of the preceding claims.
 6. A method according to claim5, wherein pumping the fluid comprising: operating the pair of pumps outof phase so as to produce a substantially continuous fluid flow.
 7. Amethod according to claim 5 wherein, pumping the fluid comprising:providing a disposable unit including a heat-exchanger component;placing the heat-exchanger component in proximity with the heatexchanger; and pumping the fluid through the heat-exchanger component soas to heat or cool the fluid in the heat-exchanger component.
 8. Amethod according to claim 7, wherein the heat-exchanger componentincludes at least one of a heat-exchanger bag, a length of tubing, and aradiator.
 9. A method according to claim 1, wherein the source is apatient and wherein the fluid is a bodily fluid.
 10. A method accordingto claim 1, further comprising: pumping the heated fluid to a patient.11. A method according to claim 10, further comprising: monitoring thepatient's temperature; and controlling operation of at least one of (a)the at least one pump and (b) the heat exchanger in order to attain apredetermined patient temperature.
 12. (canceled)
 13. A method accordingto claim 3, further comprising: providing a pneumatic actuation systemfor intermittently providing either a positive or a negative pressure tothe actuation chamber of each pump.
 14. A method according to claim 13,wherein the pneumatic actuation system is provided with: a reservoircontaining a gas at either a positive or a negative pressure, and avalving mechanism for controlling the flow of gas between the gasreservoir and the actuation chamber of each pump.
 15. A method accordingto claim 14, wherein the pneumatic actuation system is further providedwith at least one actuation-chamber pressure transducer for measuringthe pressure of the actuation chamber of each plump, and a controllerthat receives pressure information from the at least oneactuation-chamber pressure transducer and controls the valvingmechanism.
 16. A method according to claim 15, wherein the pneumaticactuation system is further provided with a reservoir pressuretransducer for measuring the pressure of the gas in the reservoir, andwherein the controller receives pressure information from the reservoirpressure transducer.
 17. A method according to claim 16, wherein thecontroller compares the pressure information from the actuation-chamberand reservoir pressure transducers to determine whether any of thepressure transducers is malfunctioning.
 18. A method according, to claim3, further comprising: providing a pneumatic actuation system foralternately providing positive and negative pressure to the actuationchamber of each pump.
 19. A method according to claim 18, wherein thepneumatic actuation system is provided with: a positive-pressure gasreservoir; a negative-pressure gas reservoir; and a valving mechanismfor controlling the flow of gas between the gas reservoirs and theactuation chamber of each pump.
 20. A method according to claim 19,wherein the pneumatic actuation system is further provided with: atleast one actuation-chamber pressure transducer for measuring thepressure of the actuation chamber of each pump, and a controller thatreceives pressure information from the at least one actuation-chamberpressure transducer and controls the valving mechanism. 21-23.(canceled)
 24. A method according to claim 20, wherein the controllercontrols the valving mechanism to cause the flexible membrane of eachpump to reach either the rigid chamber wall or the rigid limit structureat each of stroke's beginning and end, and wherein the controllerdetermines the amount of flow through each pump based on a number ofstrokes.
 25. A method according to claim 24, wherein the controllerintegrates pressure information an actuation-chamber pressure transducerover time during a stroke to detect an aberrant flow condition.
 26. Amethod according to claim 1, wherein the inlet of each pump is providedwith an inlet valve for preventing flow out of the pumping chamberthrough the inlet and the outlet of each pump is provided with an outletvalve for preventing flow into the pumping chamber through the outlet.27. A method according to claim 26, wherein the inlet valve and theoutlet valve are passive check valves.
 28. A method according to claim26, wherein the inlet valve and the outlet valve are actively controlledvalves, and wherein pumping the fluid comprises operating the valves.29. A disposable unit for use in a heat exchanger system, the disposableunit comprising: at least one reciprocating positive-displacement pump,each pump having a curved rigid chamber wall; a flexible membraneattached to the rigid chamber wall, so that the flexible membrane andrigid chamber wall define a pumping chamber; an inlet for directingfluid through the rigid chamber wall into the pumping chamber in atleast one of (a) a direction that is substantially tangential to therigid chamber wall and (b) a direction that provides low-shear flow intothe pumping chamber; and an outlet for directing fluid through the rigidchamber wall out of the pumping chamber in at least one of (a) adirection that is substantially tangential to the rigid chamber wall and(b) a direction that provides low-shear flow out of the pumping chamber;and a heat-exchanger component, in fluid communication with the at leastone pump and adapted to be received by a heat exchanger.
 30. Adisposable unit according to claim 29, wherein the heat-exchangercomponent includes at least one of a heat-exchanger bag, a length oftubing, and a radiator.
 31. A disposable unit according to claim 29,wherein each pump includes a rigid chamber wall that is hemispheroid.32. A disposable unit according to claim 29, wherein each pump includesa rigid limit structure for limiting movement of the membrane andlimiting the maximum volume of the pumping chamber, the flexiblemembrane and the rigid limit structure defining an actuation chamber.33-35. (canceled)
 36. A disposable unit according to claim 29, whereinthe inlet of each pump includes an inlet valve for preventing flow outof the pumping chamber through the inlet and the outlet of each pumpincludes an outlet valve for preventing flow into the pumping chamberthrough the outlet.
 37. A disposable unit according to claim 36, whereinthe inlet valve and the outlet valve are passive check valves.
 38. Adisposable unit according to claim 36, wherein the inlet valve and theoutlet valve are actively controlled valves.
 39. A disposable unitaccording to claim 29, wherein the heat-exchanger component includes aninlet in fluid communication with the outlet of the at least one pumpfor pumping fluid into the heat-exchanger component for heating orcooling.
 40. (canceled)
 41. A disposable unit according to claim 29,further comprising a filter in fluid communication with an outlet of theheat-exchanger component for filtering heated or cooled fluid flowingout of the heat-exchanger component.
 42. A disposable unit according toclaim 29, further comprising: a manifold including: at least one inletport for providing fluidic connection to an inlet of the heat-exchangercomponent, and an outlet port for providing fluidic connection to anoutlet of the heat-exchanger component. 43-45. (canceled)
 46. Adisposable unit according to claim 42, wherein the manifold furtherincludes at least one sensor component, each sensor component disposedin a port and capable of transmitting thermal information regardingfluid passing through the port.
 47. (canceled)
 48. A disposable unitaccording to claim 46, wherein each sensor component includes a thermalwell. 49-56. (canceled)
 57. A heat-exchanger system comprising: a heatexchanger for receiving a heat-exchanger component of a disposable unit;a pneumatic actuation system for operating at least one reciprocatingpositive-displacement pump of the disposable unit for pumping fluidthrough the heat-exchanger component, each pump including a pumpingchamber defined by a curved rigid chamber wall and a flexible membraneattached to the rigid chamber wail an further including an actuationchamber defined at least in part by the flexible membrane, the actuationchamber in fluid communication with the pneumatic actuation system; anda controller for controlling the pneumatic actuation system and the heatexchanger. 58-59. (canceled)
 60. A heat exchanger system according toclaim 57, wherein the controller is adapted to compare the temperaturereadings from the first and second locations; generate a first alarmsignal indicating faulty temperature readings, if the temperaturereading at the first location is not within a pre-set range from thetemperature reading at the second location; determine if the temperaturereading from the first or second location is above or below a pre-settemperature range; and if a reading is above or below the pre-settemperature range, generate a second alarm signal indicating thetemperature is above or below the pre-set temperature range. 61-85.(canceled)
 86. A radiator for use in a heat-exchanger system, theradiator comprising: a body including a thermally conductive material;and a channel disposed in the body for receiving a length of tubing. 87.A radiator according to claim 86, wherein the channel comprises: aninner loop; an outer loop; and a serpentine portion connecting the innerand outer loops, such that fluid flowing through portions of tubingdisposed in the inner and outer loops of the channel flow in oppositedirections.
 88. A method of moving blood between a patient-access deviceand a heat exchanger for heating the blood the method comprising:providing a reciprocating positive-displacement pump; providing a flowline having a first portion between the patient-access device and thepump and having a second portion between the pump and the heatexchanger; providing for each of the first and second portions of theflow line a valve for permitting flow in only one direction of the flowline; and actuating the pump to cause the flow of blood between thepatient-access device and the heat exchanger.
 89. A method according toclaim 88, wherein the pump is provided with a flexible membrane as areciprocating member.
 90. A method according to claim 89, wherein thepump is provided with a pneumatic actuation system for alternatelyproviding positive and negative pressure to the membrane. 91-92.(canceled)
 93. A system for extracorporeal thermal therapy, the systemcomprising: a heat exchanger for heating the blood, a reciprocatingpositive-displacement pump for moving blood between a patient-accessdevice and the heat exchanger, the pump having an inlet line and anoutlet line; a first valve, located in the inlet line, for preventingflow of blood out of the pump; and a second valve, located in the outletline, for preventing flow of blood into the pump. 94-95. (canceled) 96.A heat exchanger for heating extracorporeal blood, the heat exchangercomprising a pump, the heat exchanger comprising: a heat-exchange flowpath having an inlet and an outlet; an electricity-to-heat converterthat turns electrical power into heat for absorption by the blood; afirst temperature sensor located at the inlet for measuring thetemperature of the blood entering the heat exchanger; a secondtemperature sensor located at the outlet for measuring the temperatureof the blood exiting the heat exchanger; a metering system thatdetermines at least one of the volume or flow rate of blood passingthrough the heat exchanger; and a controller in communication with theconverter, the first and second temperature sensors, and the meteringsystem, the controller receiving information regarding at least one of:the amount of power being used by the converter, temperature informationfrom the first and second temperature sensors, flow-rate informationfrom the metering system, and volume information from the meteringsystem, the controller analyzing the received information in order todetermine whether a fault condition exists, and generating a signal if afault condition is detected.
 97. A heat exchanger for heatingextracorporeal blood for hyperthermia treatment, the heat exchangercomprising: an inlet for unheated blood; an outlet for heated blood; aflow path from the inlet to the outlet; a set of heating elementsoverlapping the flow path, including at least first and second heatingelements the second heating element being located adjacent the flow pathnear the outlet, and the first heating element being located adjacentthe flow path at a point upstream of the second heating element; a firsttemperature sensor located adjacent the flow path upstream of the firstheating element; a second temperature sensor located adjacent the flowpath between the first and second heating elements; and a controller forreceiving temperature information from the first and second temperaturesensors and for generating a signal if a temperature difference beingmeasured by the first and second sensors exceeds a limit. 98-121.(canceled)
 122. A method of heating a patient's blood, the methodcomprising; providing a heat-exchanger system for heating blood from thepatient and pumping heated blood to the patient; connecting a firsttemperature probe from the patient to the heat-exchanger system, theheat-exchanger system controlling the blood heating and pumping based ontemperature information received from the first temperature probe anddisplaying the temperature information received from the firsttemperature probe to an operator; monitoring patient temperature by theoperator using an independent second temperature probe, and terminatingthe treatment if either of the temperature probes conveys anunacceptable temperature reading.